bromochloroacetic-acid and Carcinoma--Basal-Cell

Basal cell carcinoma (BCC) is a very common tumor, of which the diagnosis is generally easy. Clinical prediction of histopathological subtype however is however often difficult, i.e. the majority of sclerosing BCCs believed to be morpheaform are in fact trabecular or nodular. There is a subgroup of aggressive BCCs, including trabecular (the most common), morpheaform (rare) and micronodular (very rare) subtypes. Differentiating trichoblastoma from BCC is not always easy, but there are distinctive histopathologic criteria and preferential expression of Berp4 in BCC and PHLDA1 in trichoblastoma that may be of help. The group of trichoblastic tumors comprises giant but benign trichoblastomas and trichoblastic carcinomas at the end of the spectrum (of low or high grade). In case of metastatic BCC, one must rule out trichoblastic carcinoma. Morphologic variants of BCC such as pigmented, clear cell, granular cell BCC or BCC with areas of keratinisation are not of poorer prognosis than the classic types. On the opposite, BCC with sebaceous differentiation (in fact sebaceomas) belong to the spectrum of tumors found in Muir-Torre and must be identified. Basosquamous BCCs should be treated like squamous cell carcinomas as they are more aggressive than the nodular subtype. Cet article fait partie du numéro supplément Prise en charge des carcinomes basocellulaires difficiles à traiter réalisé avec le soutien institutionnel de Sun Pharma.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Differentiation; Diagnosis, Differential; Humans; Keratins; Neoplasm Proteins; Neoplasms, Basal Cell; Neoplasms, Fibroepithelial; Receptors, Androgen; Skin Neoplasms; Transcription Factors

We report a case of a prostatic adenocarcinoma that showed diffuse aberrant p63 expression in the secretory cells and review the literature and differential diagnosis. p63-positive prostatic adenocarcinoma is rare and is typically encountered when working up an atypical focus with basal markers and α-methylacyl coenzyme A racemase. These carcinomas have unusual morphologic features such as atrophic cytoplasm and basaloid morphology. The differential diagnosis includes basal cell hyperplasia and basal cell carcinoma; morphologic features such as the presence of small, infiltrative acini with nuclear atypia, lack of high-molecular-weight cytokeratin expression, and positive α-methylacyl coenzyme A racemase and prostate-specific antigen expression can help distinguish a p63-positive prostatic adenocarcinoma from atypical basal cell proliferations. Current controversies regarding the grading, prognosis, and molecular profile of p63-positive prostatic adenocarcinomas are also discussed.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Proliferation; Diagnosis, Differential; Humans; Hyperplasia; Keratins; Male; Membrane Proteins; Neoplasm Grading; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Racemases and Epimerases

The cDNA microarrays allows the classification of breast cancers into 6 groups: luminal A, luminal B, luminal C, normal breast-like, human epidermal growth factor receptor 2-positive, and basal-like. This latter is characterized by the expression of basal cytokeratins (CKs), and frequent negativity for hormone receptors and human epidermal growth factor receptor 2. There is a marked parallelism between triple negative breast carcinomas and basal-like carcinoma, but these are not equivalent terms. Estimated concordance is around 80%. CK5 seems to be the best marker for the identification of these tumors. Other good markers to identify these tumors are CK14, CK17, and epidermal growth factor receptor. A subset of triple negative breast carcinomas has myoepithelial differentiation, with positivities for smooth muscle actin, p63, S-100, and CD10 among others. Recent studies suggest that basal like carcinomas are originated from mammary stem cells.

Topics: Angiogenesis Inhibitors; Animals; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Diagnosis, Differential; ErbB Receptors; Female; Humans; Incidence; Keratins; Mammary Glands, Human; Myeloid Progenitor Cells; Receptors, Cell Surface

The introduction of global gene expression analysis in breast cancer research has focused attention onto a repeatedly described subgroup of invasive breast cancer, the basal-like carcinomas. This subgroup is characterised by the expression of high-molecular weight cytokeratins 5, 14 and 17; using immunohistochemical diagnosis, it represents approximately 7-20% of invasive breast cancers. Some of these tumours fulfil the criteria of grade 3 invasive ductal carcinoma, the so-called triple negative carcinomas. However, other rare subgroups of metaplastic, medullary and myoepithelial carcinomas also belong to this entity. Even though the initial clinical prognostic relevance of basal-like breast cancers may have been overestimated, its distinctive biology generates many questions regarding the pathogenesis, chemosensitivity and optimal clinical management of this subgroup. Physiological progenitor cells within the normal female breast share essential immunohistochemical features with basal-like breast cancers. Although the exact relationship between subgroups of normal breast cells and their respective malignant counterparts is still under investigation, the major hallmarks of physiological progenitor cells are either maintained or reactivated by distinct genetic changes in basal breast cancer cells. This review will discuss the impact of these findings on our global understanding of breast cancer pathogenesis, especially from the perspective of its potential histogenesis. Clinical consequences and potential future research directions driven by the definition of basal breast cancers will also be discussed.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Basal Cell; Carcinoma, Ductal, Breast; Female; Genotype; Humans; Immunophenotyping; Keratins; Neoplastic Stem Cells

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Basal Cell; Carcinosarcoma; Female; Histone Deacetylases; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin Neoplasms; Telomerase; Vimentin

Recent publications have classified breast cancers on the basis of expression of cytokeratin-5 and -17 at the RNA and protein levels, and demonstrated the importance of these markers in defining sporadic tumours with bad prognosis and an association with BRCA1-related breast cancers. These important observations using different technology platforms produce a new functional classification of breast carcinoma. However, it is important in developing hypotheses about the pathogenesis of this tumour type to review the nomenclature that is being used to emphasize potential confusion between terminology that defines clinical subgroups and markers of cell lineage. This article reviews the lineages in the normal breast in relation to what have become known as the 'basal-like' carcinomas.

Topics: Breast; Breast Neoplasms; Carcinoma, Basal Cell; Epithelial Cells; Female; Gene Expression Profiling; Humans; Immunohistochemistry; Keratins; Prognosis

We describe a case of pulmonary carcinoma with myoepithelial differentiation, analogous to basal cell adenocarcinoma of salivary glands. The patient, a 60 year-old man, smoker, presented with three peripheral nodules of the left lung. Preoperative staging was negative for metastatic disease and the patient underwent a surgical resection of the nodules. After 22 months, the patient is alive with no evidence of disease. Microscopically, the tumours were composed of atypical cells arranged in lobules, separated by basal membrane-like material. Immunohistochemically, tumour cells were positive for cytokeratin AE1/AE3, cytokeratin 14, vimentin, calponin, S-100 protein and gliofibrillary acid protein (GFAP). Electron microscopy showed features of epithelial and myoid differentiation and confirmed the myoepithelial nature of the tumour. Pulmonary tumours with myoepithelial differentiation are rare, but they have a wide and distinctive morphological spectrum.

Topics: Basement Membrane; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Carcinoma, Basal Cell; Carcinoma, Non-Small-Cell Lung; Cell Differentiation; Epithelium; Glial Fibrillary Acidic Protein; Humans; Keratins; Lung Neoplasms; Male; Microfilament Proteins; Microscopy, Electron; Middle Aged; Myoepithelioma; Neoplasm Proteins; Organ Specificity; Remission Induction; S100 Proteins; Salivary Gland Neoplasms; Staining and Labeling; Vimentin

A case of basal cell carcinoma with giant cells of the central epithelial and surrounding stromal components is presented. The lesion was an 8-mm dome-shaped papule on the ear of a 66-year-old man. The giant cells of the epithelial component shared the immunophenotype of the more typical cells of the basal cell carcinoma (keratin, smooth muscle actin, and bcl-2 positive), whereas the stromal giant cells were positive only for bcl-2. This case represents a peculiar variant of pleomorphic basal cell carcinoma, the significance of which is unknown.

Topics: Actins; Aged; Carcinoma, Basal Cell; Epithelial Cells; Female; Giant Cells; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Muscle, Smooth; Proto-Oncogene Proteins c-bcl-2; Skin Neoplasms; Stromal Cells

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Keratinocytes; Keratins; Reference Values; Skin Neoplasms

A 63-year-old man presented with a signet ring cell basal cell carcinoma of the right infraorbital area. This is the third reported case of this rare variant of basal cell carcinoma characterized by tumor cells containing large, hyalinized, eccentric, intracytoplasmic inclusions that compress nuclei into crescent or ring-shaped forms. Antibodies to both high and low molecular weight cytokeratins were strongly positive, staining the inclusions in a uniform fashion. Vimentin and actin antibodies did not stain the inclusions. These results support previous electron microscopic studies that show the inclusions to be aggregates of intermediate filaments blending into tonofilaments at their periphery. Although speculative, the formation of signet ring cells does not appear to be a degenerative or necrotic phenomenon, but probably a peculiar aberrant form of individual cell keratinization.

Topics: Carcinoma, Basal Cell; Diagnosis, Differential; Facial Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged

The cellular characteristics of the basilar epithelium in Warthin's tumor have had limited investigation. Ultrastructural examination of basal cells in 9 Warthin's tumors reveals that in addition to numerous mitochondria these cells possess a rich complement of tonofilaments. However, in three examples there are a proportion of these tonofilament-rich cells that have a narrow band of microfilaments in the peripheral cytoplasm adjacent to the basal lamina. Frozen sections of Warthin's tumor and normal salivary glands, doubly labeled with rhodamine-phalloidin for actin and monoclonal antibody 312C8-1 for cytokeratin 14, show that normal myoepithelial cells of acini and intercalated ducts have both of these filaments, as do a proportion of basal cells in the tumor. There are distinct differences in the cytokeratin polypeptide complement between normal luminal and myoepithelial cells as well as between luminal and basal cells in Warthin's tumor. Differences occur in the cytokeratin profiles between the luminal and basal cells of Warthin's tumor and comparable cells in the normal gland; however, there continue to be some similarities in the cytokeratin polypeptides of myoepithelium and the basal cells of normal salivary ducts and the basal cells of Warthin's tumor. These findings show that basal cells in Warthin's tumor are a mixed population with some capable of differentiating as myoepithelial-like cells, and that this tumor could arise from any level of the normal salivary gland duct system.

Topics: Adenolymphoma; Antibodies, Monoclonal; Carcinoma, Basal Cell; Cytoplasmic Granules; Epithelium; Humans; Immunohistochemistry; Keratins; Microfilament Proteins; Microscopy, Fluorescence; Salivary Gland Neoplasms; Staining and Labeling

Topics: Adenocarcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cells, Cultured; Digestive System Neoplasms; Epithelium; Female; Histocytochemistry; Humans; Keratins; Molecular Weight; Neoplasms

A 10-year-old female rabbit developed an unencapsulated and asymmetrical superficial dermal mass on the neck. The tumour was invasive with central ulceration and contained three different histological components, namely trichoblastomatous, basal cell carcinoma (BCC)-like and undifferentiated carcinomatous. In the trichoblastomatous component, which occupied most of the tumour, epithelial neoplastic cells formed ribbon-like cellular trabeculae with a palisaded appearance and stromal giant cells. The BCC-like component was a unique lesion composed of epithelial foci and sarcomatous stroma. The sarcomatous stroma consisted of pleomorphic mesenchymal cells with collagen fibres and frequent giant cells with one or more bizarre nuclei. In the undifferentiated carcinomatous component, neoplastic cells had a sheet-like growth pattern without trichoblastic or squamous differentiation. Immunohistochemically, neoplastic epithelial cells were positive for p63 and cytokeratin (CK) while the stromal and giant cells were immunopositive for vimentin but negative for CK and p63. This is the first report of a malignant trichoblastoma with a sarcomatous stroma in animals.

Topics: Animals; Carcinoma, Basal Cell; Epithelial Cells; Female; Keratins; Rabbits; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms

Consistent with cancer stem cell driven pattern of growth, human basal cell carcinomas (BCCs) demonstrate differentiation along hair follicle (HF) lineages.. To define the pattern of differentiation and therapeutic targets that promote BCC differentiation and therefore BCC cancer stem cell exhaustion.. An alkaline phosphatase substrate kit was used to determine dermal papilla cells within the BCC stroma. Autonomous HF cycle-dependent gene expression was identified by analysis of the human homologues of a murine gene set (total 2289 genes) that is differentially expressed in hair cycle phases. The findings were validated by quantitative real-time PCR and immunofluorescence, as well as in vitro transforming growth factor (TGF)-β2 stimulation of BCC cancer stem cell colonies.. As in the HF, keratin expression in the inner root sheath and matrix in BCC correlated with proliferative index and was tightly regulated, despite the absence of dermal papilla cells. Cross-species microarray analysis comparing human BCC and murine synchronous HF growth cycle datasets revealed 74% concordance with telogen differentiation compared with anagen (23%, P < 0.01) and catagen (49%; P < 0.01). Incomplete anagen differentiation within BCC was characterized by reduced expression of the anagen master regulator DLX3 (-5.5-fold), and increased expression of telogen-associated genes: AEBP1 (2.2-fold), DEFB8 (35.3-fold), MMP3 (106.0-fold) and MMP12 (12.9-fold). Restoration of dermal papilla signals by in vitro addition of TGF-β2 enhanced anagen differentiation.. Our findings show that BCC cells differentiate along HF lineages and may be susceptible to exogenous HF cycle modulators.

Topics: Animals; Carcinoma, Basal Cell; Cell Differentiation; Cell Transformation, Neoplastic; Fluorescent Antibody Technique; Gene Expression; Hair Follicle; Humans; Keratins; Mice; Oligonucleotide Array Sequence Analysis; Real-Time Polymerase Chain Reaction; Skin Neoplasms

Neoplasms consisting of different cell lineages within a single skin specimen are rare, yet well documented in the literature. However, to date, there appears to be no report of invasive melanoma arising directly from the passenger melanocytes of a basal cell carcinoma (BCC). We present a case of a 91-year-old male with a suspicious lesion on the ear. Histopathology and immunohistochemical staining revealed BCC closely intertwined with invasive melanoma that exhibited foci of chondroid differentiation. The melanoma appeared to arise from the benign-appearing passenger melanocytes of the BCC and lacked connection to the overlying epidermis or an in situ component. Multiple dermatopathologists reviewed the case and agreed that the most likely explanation for the histopathologic findings was that the invasive melanoma arose from the passenger melanocytes within the BCC.

Topics: Aged, 80 and over; Carcinoma, Basal Cell; Ear Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Melanocytes; Melanoma; Melanoma, Cutaneous Malignant; Neoplasm Invasiveness; Neoplasms, Multiple Primary; S100 Proteins; Skin Neoplasms; SOXE Transcription Factors; Treatment Refusal

Cutaneous carcinosarcoma is a rare biphasic tumor comprising malignant epithelial and heterologous mesenchymal elements. Data on the clinical and histopathologic characteristics of this tumor in Asian populations are not available. The purpose of this study was to investigate the clinicopathologic and immunohistochemical features of cutaneous carcinosarcoma in the Korean population.. We retrospectively reviewed the records of 11 patients with cutaneous carcinosarcoma who were diagnosed from 2006 to 2016.. The mean patient age at diagnosis was 71.5 years (range, 43-96 years) and there was a men predilection. The most common site of cutaneous carcinosarcoma was the head and neck (8/11, 72.7%). Histopathologically, most tumors showed a characteristic morphology consisting of two types of tumor cells, varied differentiated epithelial cells (such as basal or squamous cells) and spindle cells with transition zones between the two components. These two cell types also demonstrated variable immunohistochemical characteristics.. Although the number of cases in this study was limited, our results provide valuable insight into the clinical and histopathologic characteristics of cutaneous carcinosarcoma in the Korean population.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carcinosarcoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Republic of Korea; Retrospective Studies; Tumor Suppressor Protein p53

Perineural invasion (PNI) is associated with high risk keratinocyte carcinomas. Identification of PNI during Mohs surgery is important for staging and post-adjuvant treatment decisions but can be challenging. To confirm or exclude PNI suspected on hematoxylin and eosin sections, we performed immunohistochemical double staining on Mohs frozen sections. Neural marker SOX10 and pan-cytokeratin marker AE1/AE3 were combined in a simultaneous assay using species-specific (mouse and rabbit) antibodies and horseradish peroxidase and alkaline phosphatase detection systems. Of 23 Mohs cases with suspected PNI, 18 were confirmed to have definitive nerve involvement by tumor using double staining. Double staining frozen tissue is feasible and can be beneficial for real time confirmation of PNI during Mohs.\ \ J Drugs Dermatol. 2019;18(3):262-264.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Frozen Sections; Humans; Immunohistochemistry; Keratins; Mohs Surgery; Neoplasm Invasiveness; Peripheral Nerves; Skin; Skin Neoplasms; SOXE Transcription Factors

Basal cell carcinoma (BCC) seems to originate from ultraviolet light-induced mutations involving the bulge or the outer sheath of the hair follicle cells. However, the etiopathogenic mechanisms involved in the development of these tumors in nonphotoexposed and in hairless areas remain unclear. The cytokeratin (CK) profile (including CK5/6, CK7, CK14, CK15, CK17, and CK19) from a series of different BCC subtypes developing in sun-exposed and non-sun-exposed areas, including hairless regions, was evaluated. The authors have observed that CK7 expression in BCC is associated with the anatomical localization of the tumor and its sun-exposition, but not with other factors such as histological subtype. The expression of this CK is higher in BCCs located in non-sun-exposed and nonhairy areas, such as the vulvar semimucosa and the nipple. Because CK7 is a marker of simple glandular epithelia, the authors suggest a glandular origin for BCCs located in hairless and nonphotoexposed areas.

Topics: Adult; Carcinoma, Basal Cell; Female; Hair Follicle; Humans; Keratins; Male; Neoplasms, Adnexal and Skin Appendage; Skin Neoplasms; Sunlight

The diagnosis of cutaneous epithelial tumors (CETs) in dogs is based on predominant histological differentiation patterns. However, the expression of a broad panel of antigens has not been comprehensively examined with immunohistochemistry. The present study aims to establish a comprehensive expression profile and identify useful diagnostic markers for each CET type. Cytokeratin (CK), stem cell, and other associated markers were immunohistochemically examined in 110 canine CETs. Among these, CK16 was useful for differentiating between basal and squamous cell carcinomas. Acantholytic squamous cell carcinomas were positive for CK8, CK18, and CK19, suggesting their close association with the apocrine duct. Unlike their benign counterparts, sebaceous carcinomas coexpressed CK5/6 and adipophilin. Smooth muscle actin (SMA) and p63 immunostaining were useful for accurately distinguishing between glandular and ductal differentiation in apocrine tumors. A case of apocrine carcinoma and malignant myoepithelioma was identified using anti-SMA antibodies. Stem cell expression profiles (CK8, CK15, CK19, and CD34) of hair follicle tumors were discrete and indicative of their anatomic origins. The effectiveness of immunohistochemistry for tumor diagnosis was further confirmed by hierarchical cluster analysis, through which selected markers were able to sort CETs into specific groups: CK5/6, CK8, CK14, CK16, CK18, CK19, p63, adipophilin, and SMA sorted tumors of epidermal, apocrine, or sebaceous origin; while CK8, CK14, CK15, CK16, CK19, CD34, and p63 sorted hair follicle tumors in agreement with their histological differentiation. In conclusion, the present study provides comprehensive immunohistochemical information, which could complement histomorphological features for the future classification of canine CETs.

Topics: Animals; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cluster Analysis; Dog Diseases; Dogs; Epithelial Cells; Keratin-18; Keratin-19; Keratin-8; Keratins; Skin; Skin Neoplasms; Stem Cells

Morpheaform basal cell carcinoma (BCC) is a variant of BCC characterized by narrow strands and nests of basaloid cells with dense sclerotic stroma. The histologic extent often exceeds the clinical impression, leading to high recurrence rates after standard excision. The authors encountered a case with single-cell invasion distant from the main tumor. To date a systematic review of single-cell infiltration in morpheaform BCC has yet to be performed.. Ten morpheaform BCCs, 10 nonmorpheaform aggressive BCCs, 5 desmoplastic trichoepitheliomas, and 2 microcystic adnexal carcinomas were identified by database search and confirmed on hematoxylin and eosin. Cases were evaluated by hematoxylin and eosin, immunohistochemical staining for p63, and (in a subset) broad-spectrum cytokeratin. Single-cell pattern was defined as individual cells, 2-cell clusters, or single-file invasion.. Three types of single-cell pattern were identified: intratumoral (single cells within the main tumor mass), peripheral, and distant. Single cells were typically a minor component relative to larger tumor nodules and strands. Eight of the 10 cases of morpheaform BCC demonstrated areas of single-cell pattern: 3 intratumoral, 3 peripheral, and 2 with distant spread (0.75 and 1.0 mm from the main tumor). Eight of the 10 aggressive BCC demonstrated a peripheral single-cell pattern. Rare intratumoral single cells were identified in 3/5 desmoplastic trichoepitheliomas and 1/2 microcystic adnexal carcinomas.. Single-cell pattern is frequently a component of morpheaform BCC. Tumor cells at a significant distance from the main component were unique to morpheaform BCC. Thus, when evaluating margins for morpheaform BCC, increased caution is recommended, and immunohistochemical stains for p63 or cytokeratins may be helpful.

Topics: Biomarkers, Tumor; Biopsy; Carcinoma, Basal Cell; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Predictive Value of Tests; Skin Neoplasms; Transcription Factors; Tumor Suppressor Proteins

The application of immunocytochemistry in the field of Mohs micrographic surgery (MMS) is well established. This study evaluates the use of pan-cytokeratins (AE1/AE3, MNF116 and AE1/AE3+PCK26) in the assessment of basal cell carcinoma (BCC) on frozen tissue debulk specimens. Fifty-five cases of BCC, all from head and facial sites, were assessed in the study. In addition to staining all cases for the three cytokeratin antibodies under investigation, sections were also stained with haematoxylin and eosin (H&E) to demonstrate tumour architecture and morphology. All sections for immunocytochemistry were stained on a Roche Ventana BenchMark Ultra automated platform employing a rapid frozen section protocol. Results were assessed based on the intensity of staining of keratinocytes (scale: 0-100%), as well as sensitivity of staining determined by the total percentage of keratinocytes stained within the tissue section. AE1/AE3 demonstrated the most consistent staining both in terms of intensity of staining and sensitivity, with a mean of 99.1% and 99.9%, respectively. AE1/AE3+PCK26 average results indicated scores of 70.6% for intensity and 87.2% for sensitivity, with MNF116 scoring 92.9% for intensity but only 57.3% for sensitivity. The data indicate that AE1/AE3 is the best pan-cytokeratin antibody to use in the assessment of BCC in MMS. The use of cytokeratin immunocytochemistry is justified in morphologically complex cases of BCC, or in cases where dense inflammatory infiltrate surrounding any suspicious cells make identification of small numbers of tumour cells difficult to determine with just an H&E stain. The significant rationale is that cytokeratin staining is a valuable adjunct in the study of tumour cell assessment in cases of MMS for BCC. In addition, the use of anti-AE1/AE3 cytokeratin antibodies provides the most consistent staining results for such cases.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Facial Neoplasms; Frozen Sections; Humans; Immunohistochemistry; Keratins; Mohs Surgery; Sensitivity and Specificity; Skin Neoplasms

Apocrine poromas are rare and distinctive benign adnexal neoplasms featuring tumor cells differentiating toward folliculosebaceous-apocrine units. We report an extremely rare case with multiple apocrine poromas in a single patient. Fifteen tumors were distributed on the head, neck, forearm and axilla of a 74-year-old man. All tumors were mostly composed of poroid cells that surrounded variably sized duct spaces, some of which exhibited decapitation secretion. The poroid cells were continuous with infundibulum-like structures that contained aggregates of mature sebocytes. The patient had no family history of similar tumors and no history of immunosuppressive therapy. This is the first report of multiple apocrine poromas, suggesting that predisposing genetic factors might play a part in the development of the tumors.

Topics: Aged; Apocrine Glands; Biomarkers; Carcinoma, Basal Cell; Diagnosis, Differential; Humans; Keratin-7; Keratins; Male; Poroma; Sweat Gland Neoplasms

Topics: Animals; Biopsy, Fine-Needle; Carcinoma, Basal Cell; Diagnosis, Differential; Dog Diseases; Dogs; Female; Immunohistochemistry; Keratinocytes; Keratins; Skin Neoplasms

Topics: Aged, 80 and over; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Skin Neoplasms; Tumor Suppressor Protein p53

Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

Topics: Animals; Antigens, CD; Carcinoma, Basal Cell; Cell Differentiation; Cell Proliferation; Humans; Keratins; Kruppel-Like Factor 4; Mice; Mice, Inbred NOD; Mice, Nude; Mice, SCID; Receptors, G-Protein-Coupled; Skin Neoplasms; Smoothened Receptor; Transplantation, Heterologous; Tumor Stem Cell Assay

Sarcomatoid basal cell carcinoma (BCC) is rare. In the literature, data on the prognosis of such a variant is somewhat contradictory. D2-40 immunoexpression has been shown to have prognostic connotations in carcinomas of organs other than the skin. However, although D2-40 immunoexpression has been investigated in "common" (nonsarcomatoid) BCC, it has not yet been studied in the spindle cell component of a sarcomatoid BCC. We present a sarcomatoid BCC on the neck of an 87-year-old man that has grown rapidly over the last few months. The sarcomatoid component of the tumor expressed several types of cytokeratins, such as AE1/AE3, CK 5/6, 34betaE12, and CAM 5.2. It was also positive for p63 and for D2-40 in a diffuse pattern.

Topics: Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Basal Cell; Gene Expression; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Metaplasia

For rapid, intra-operative pathological margin assessment to guide staged cancer excisions, multimodal confocal mosaic scan image wide surgical margins (approximately 1 cm) with sub-cellular resolution and mimic the appearance of conventional hematoxylin and eosin histopathology (H&E). The goal of this work is to combine three confocal imaging modes: acridine orange fluorescence (AO) for labeling nuclei, eosin fluorescence (Eo) for labeling cytoplasm, and endogenous reflectance (R) for marking collagen and keratin. Absorption contrast is achieved by alternating the excitation wavelength: 488 nm (AO fluorescence) and 532 nm (Eo fluorescence). Superposition and false-coloring of these modes mimics H&E, enabling detection of cutaneous squamous cell carcinomas (SCC). The sum of mosaic Eo+R is false-colored pink to mimic the appearance of eosin, while the AO mosaic is false-colored purple to mimic the appearance of hematoxylin in H&E. In this study, mosaics of 10 Mohs surgical excisions containing invasive SCC, and five containing only normal tissue were subdivided for digital presentation equivalent to 4 × histology. Of the total 50 SCC and 25 normal sub-mosaics presented, two reviewers made two and three type-2 errors (false positives), respectively. Limitations to precisely mimic H&E included occasional elastin staining by AO. These results suggest that confocal mosaics may effectively guide staged SCC excisions in skin and other tissues.

Topics: Absorption; Acridine Orange; Artifacts; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Collagen; Cytoplasm; Eosine Yellowish-(YS); False Positive Reactions; Humans; Keratins; Microscopy, Confocal; Mohs Surgery; Neoplasm Invasiveness; Reproducibility of Results; Skin; Skin Neoplasms

Peripheral ameloblastoma (PA) is a rare extraosseous odontogenic tumor with histological characteristics similar to those of the common intraosseous ameloblastoma. Two questions regarding PA remain: its histogenic origin and how to differentiate between PA and intraoral basal cell carcinoma. We describe a patient with PA. The result of immunohistochemistry showed cytokeratin (CK) 7-, CK14+, CK19+, AE1/AE3+, CAM5.2-, 34 β E12+, epithelial membrane antigen-, Ber-EP4-, p53-, p63+, and low Ki-67, that was similar to those of 4 cases of intraosseous ameloblastoma. Our results suggest that a PA originates from odontogenic epithelial remnants, rather than from the oral epithelium.

Topics: Ameloblastoma; Antiporters; Biomarkers, Tumor; Carcinoma, Basal Cell; Diagnosis, Differential; Gingival Neoplasms; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Middle Aged; Molar; Mucin-1; Tumor Suppressor Protein p53

Adenoid basal hyperplasia is an underrecognized cervical lesion, resembling adenoid basal carcinoma, except the absence of deep invasion into the stroma. We report a series of 10 cases, all extending less than 1 mm from the basement membrane. Our results support the hypothesis that adenoid basal hyperplasia arises from reserve cells of the cervix. Lesions were found close to the squamocolumnar junction, in continuity with the nearby subcolumnar reserve cells. They shared the same morphology and immunoprofile using a panel of 4 antibodies (keratin 5/6, keratin 14, keratin 7 and p63) designed to differentiate reserve cells from mature squamous cells and endocervical columnar cells. We detected no human papillomavirus infection by in situ hybridization targeting high-risk human papillomavirus, which was concordant with the absence of immunohistochemical p16 expression. We demonstrated human papillomavirus infection in 4 (80%) of 5 adenoid basal carcinoma, which is in the same range as previous studies (88%). Thus, adenoid basal hyperplasia should be distinguished from adenoid basal carcinoma because they imply different risk of human papillomavirus infection and of subsequent association with high-grade invasive carcinoma. In our series, the most reliable morphological parameters to differentiate adenoid basal hyperplasia from adenoid basal carcinoma were the depth of the lesion and the size of the lesion nests. Furthermore, squamous differentiation was rare in adenoid basal hyperplasia and constant in adenoid basal carcinoma. Finally, any mitotic activity and/or an increase of Ki67 labeling index should raise the hypothesis of adenoid basal carcinoma.

Topics: Adult; Aged; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Cervix Uteri; Epithelial Cells; Female; Humans; Hyperplasia; Keratins; Middle Aged; Uterine Cervical Neoplasms

Infundibulocystic basal cell carcinoma (IBCC) is a variant of basal cell carcinoma. Sporadic cases usually represent a solitary tumor and multiple IBCC is rare. There have been no reports in which the tumor differentiation is characterized immunohistochemically. We report a case of multiple IBCC which developed on a patient's scalp by performing histopathological and immunohistochemical examinations, using monoclonal antibodies against cytokeratins (CKs). A 76-year-old female had noticed multiple small papules on her scalp. She noticed that the tumors were growing when she underwent systemic chemotherapy for metastatic lung cancer. Routine histopathological specimens from skin biopsies revealed findings typical of IBCC. The tumor cells expressed CK14 and CK17. However, CK1 and CK10 were expressed only in a few cells in the inner area of the tumors. The present case is unique in two points. First, multiple tumors developed on the patient's scalp during the systemic chemotherapy for the lung cancer. Second, the tumor showed CK expression patterns characteristic to infundibular and trichilemmal epithelia.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carboplatin; Carcinoma, Basal Cell; Docetaxel; Female; Humans; Immunohistochemistry; Irinotecan; Keratins; Lung Neoplasms; Neoplasms, Second Primary; Skin Neoplasms; Taxoids

Current treatments for nonmelanoma skin cancer include surgery, Mohs micrographic surgery, radiation, cryosurgery, photodynamic therapy, local chemotherapy and application of immunomodulators such as imiquimod. However, all have a 5-year recurrence rate of 1-40%. Gene therapy for the treatment of skin cancers is a promising new approach, as delivery of the vectors to the skin is simple and safety issues can be properly addressed.. To develop an ex-vivo organ culture system for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) tumours, and to test the feasibility of applying oncolytic viruses to these tumours.. We first optimized conditions for the maintenance of BCC and SCC tissues in organ culture, and demonstrated viability of the tissues ex vivo for 3-7 days. The tropism of two potential oncolytic viral vectors, herpes simplex virus type 1 (HSV-1) and adenovirus (AD), was next evaluated.. Immunohistological analysis revealed that HSV-1 targeted tumour cells that expressed p63 and did not express keratin 15 or keratin 14 markers of keratinocytes. Further examination indicated that uninfected BCC and SCC tissues express two isoforms of p63 mRNA, and HSV-1 infection specifically enhanced expression of the TAp63 isoform. Furthermore, following infection, both HSV-1 and AD induced apoptosis in the BCC and SCC cells as indicated by the induction of activated caspase-3.. The results indicated a specific pattern of viral tropism to skin cancer cells that are critical for maintenance of the tumour. This new experimental system should aid in the analysis of new therapeutic modalities, such as oncolytic viruses, for future treatment of these skin tumours.

Topics: Adenoviridae; Apoptosis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Caspase 3; Herpesvirus 1, Human; Humans; Immunohistochemistry; Keratinocytes; Keratins; Organ Culture Techniques; Skin Neoplasms; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Viral Tropism

This study examined immunohistochemical findings of sebaceous carcinoma and sebaceoma. An immunohistochemical study using 13 anti-cytokeratin (CK) antibodies (anti-CK1, 5-8, 10 and 14-20) and 35 cases of sebaceous carcinoma (16 cases on ocular and 19 cases on extraocular regions) and 10 cases of sebaceoma (no cases arose on the eyelids) was performed. Overall, those in ocular lesions were almost the same as those for extraocular lesions in sebaceous carcinoma other than CK8. The findings in sebaceous carcinoma were almost equal to those of sebaceoma. Over 75% of cases with sebaceous carcinoma were positive with anti-CK5 and anti-CK14 antibodies and negative with anti-CK1, CK10, CK15, CK17, CK18 and CK20 antibodies. Most cases (50-75%) of those were positive with CK7 and negative with CK6, CK16, CK19 and CK8. The sensitivity and specificity of immunohistochemical detection of sebaceous carcinoma using the panel of anti-cytokeratin antibodies were lower than those of other antibodies. Immunohistochemical detection of cytokeratins in diagnosing sebaceous carcinoma should be considered to be ancillary to conventional microscopic findings and those of other antibodies.

Topics: Adenocarcinoma, Sebaceous; Antibodies, Monoclonal; Carcinoma, Basal Cell; Diagnosis, Differential; Eyelid Neoplasms; Humans; Immunohistochemistry; Keratins; Sebaceous Gland Neoplasms

Prostatic gland basal cell proliferations exhibit morphological continuum ranging from basal cell hyperplasia to basal cell carcinoma. In the following report, we described clinical features, morphological spectrum, neuroendocrine differentiation and histogenesis of prostatic gland basal cell carcinoma in our patient.. Hematoxylin-eosin (HE), Alcian blu-periodic acid schiff (AB-PAS) at pH 2.5 stained sections and the avidin-biotin-peroxidase complex (ABC), were performed on prostate gland paraffin-embedded tissue. Monoclonal antibodies directed against cytokeratin (34betaE12) which selectively stains basal cells, prostate specific antigen (PSA), chromogranine A, neuron-specific enolase (NSE), synaptophysin and CD56, were used. Basal cell proliferations exhibited a morphological continuum ranging from basal cell hyperplasia to prostatic gland carcinoma. In these prostatic lesions, positive reactivity was demonstrated for 34betaE12 and CD56. These findings indicate that the basaloid cells of basal cell hyperplasia, florid basal cell hyperplasia, atypical basal cell hyperplasia and basal cell carcinoma are derived from basal cells of the normal prostate gland suggesting a continuum in the progression of hyperplasia to benign and then malignant neoplasia. The presence of CD56 protein in the discovered lesions may be related to their neuroendocrine differentiation.. The fact, that our patient was well six years after the radical prostatectomy supports the belief of some authors that basal cell carcinoma represents a low grade carcinoma with an excellent prognosis.

Topics: Carcinoma, Basal Cell; CD56 Antigen; Cell Differentiation; Cell Proliferation; Chromogranin A; Humans; Keratins; Male; Middle Aged; Neuroendocrine Cells; Phosphopyruvate Hydratase; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Synaptophysin

We investigated the staining pattern of commonly used basal cell/myoepithelial markers, such as p63 (a p53-homologous nuclear protein), basal cell-specific cytokeratin antibody (34betaE12, K903), and smooth muscle myosin heavy chain (SMMHC) in benign and malignant bronchioloalveolar proliferations of the lung. We studied 85 lung lesions consisting of 35 bronchioloalveolar carcinoma, 30 well-differentiated adenocarcinoma, and 20 cases of benign lung lesions. In normal lung, p63, K903, and SMMHC decorated the basal cells of large and small airways and occasional cells of terminal bronchioles. In reactive processes, a distinctive staining pattern was present in 19/20 (95%) of the cases characterized by staining of basal cells of the airways and bronchiolar epithelium and squamous metaplastic epithelium for p63 and K903, whereas 12/20 (60%) stained with SMMHC. Respiratory ciliated cells, alveolar epithelial cells, and nonepithelial cells were negative. In bronchioloalveolar carcinoma, a discontinuous peripheral rim of p63-immunoreactive cells was retained surrounding and intermingled with the malignant bronchioloalveolar proliferation in 31/35 (88.5%) cases, SMMHC in 28/35 (80%) cases, and K903 in 20/35 (57%) cases. For adenocarcinoma, a majority of the cases (28/30, 93%) were negative for p63 and K903; however, SMMHC showed artifactual staining in the desmoplastic stroma in 6/30 (20%) cases. Our results highlighted the differential expression of basal cell markers across various bronchioloalveolar lesions. The staining pattern of basal cells in bronchioloalveolar carcinoma supports that these neoplasms may actually be carcinoma in-situ.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Membrane Proteins; Middle Aged; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Smooth Muscle Myosins

Keratocystic odontogenic tumor is a cystic lesion that behaves more aggressively than other jaw cysts. One of its characteristic histologic features is a parakeratinized uniform layer of lining epithelium. A jaw cyst lined with orthokeratinized epithelium is called an orthokeratinized odontogenic cyst. These keratinized jaw cysts are thought to be separate entities, although their histopathogenesis has not been fully assessed. To better understand these lesions, we performed comprehensive immunohistochemical profiling of the keratin expression of each. Orthokeratinized odontogenic cysts expressed keratin 1, keratin 2, keratin 10, and loricrin, suggesting differentiation toward normal epidermis. Keratocystic odontogenic tumors expressed keratin 4, keratin 13, keratin 17, and keratin 19, which is a unique expression pattern reminiscent of a mucosal squamous epithelium and an epithelial appendage. In neonatal rat tooth germ, cells strongly positive for keratin 17 and keratin 19 were observed, specifically in the dental lamina, implying the origin of keratocystic odontogenic tumor. GLI2, a downstream effector of hedgehog signaling, was significantly expressed in keratocystic odontogenic tumor and basal cell carcinoma, accompanied with robust expression of keratin 17, mammalian target of rapamycin, and BCL2. The expression of these GLI2- or keratin 17-related factors was not significantly observed in orthokeratinized odontogenic cysts. These findings provide evidence to support the viewpoint that keratocystic odontogenic tumor and orthokeratinized odontogenic cyst are separate entities, and furthermore suggest their characteristic histology, pathogenesis, and biological behaviors.

Topics: Adolescent; Adult; Aged; Animals; Animals, Newborn; Carcinoma, Basal Cell; Child; Epithelial Cells; Female; Fluorescent Antibody Technique, Indirect; Humans; Jaw Neoplasms; Keratins; Kruppel-Like Transcription Factors; Male; Membrane Proteins; Middle Aged; Nuclear Proteins; Odontogenic Cysts; Odontogenic Tumors; Proto-Oncogene Proteins c-bcl-2; Rats; TOR Serine-Threonine Kinases; Young Adult; Zinc Finger Protein Gli2

Basaloid skin tumors, including basal cell carcinoma (BCC) and basaloid follicular hamartoma, are associated with aberrant Hedgehog (Hh) signaling and, in the case of BCC, an expanding set of genetic variants including keratin 5 (encoded by KRT5), an intermediate filament-forming protein. We here show that genetic ablation of keratin 17 (Krt17) protein, which is induced in basaloid skin tumors and co-polymerizes with Krt5 in vivo, delays basaloid follicular hamartoma tumor initiation and growth in mice with constitutive Hh signaling in epidermis. This delay is preceded by a reduced inflammation and a polarization of inflammatory cytokines from a Th1- and Th17-dominated profile to a Th2-dominated profile. Absence of Krt17 also attenuates hyperplasia and inflammation in models of acute dermatitis. Re-expression of Krt17 in Gli2(tg); Krt17(-/-) keratinocytes induces select Th1 chemokines that have established roles in BCC. Our findings establish an immunomodulatory role for Krt17 in Hh driven basaloid skin tumors that could impact additional tumor settings, psoriasis and wound repair.

Topics: Animals; Blotting, Western; Carcinoma, Basal Cell; Ear; Epithelial Cells; Female; Hamartoma; Hedgehog Proteins; Hyperplasia; Immunoprecipitation; Keratinocytes; Keratins; Kruppel-Like Transcription Factors; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Skin Neoplasms; Zinc Finger Protein Gli2

Breast cancer in the young is considered a special clinical presentation of the disease. Sixty-nine breast cancer cases diagnosed at or before the age of 35 were analyzed for common morphological and immunophenotypical features of basal-like carcinomas. Sixteen carcinomas displayed the immunophenotypical characteristics (estrogen receptor and HER2 negativity and positivity for at least one of the following basal markers: cytokeratin 5 or 14, epidermal growth factor receptor, p63) of basal-like carcinomas, and most of them demonstrated characteristic histological features (pushing borders, lymphocytic peritumoral infiltrate, central hypocellular zone or necrosis, high mitotic rate) too. These tumors were more likely to be high-molecular-weight cytokeratin: 34betaE12 and p53 positive by immunohistochemistry. The presence of a basal-like phenotype can be important as concerns systemic treatment issues and could theoretically be associated with a higher rate of BRCA1 mutations in the young, because of the overlap of BRCA1 mutation associated breast carcinomas and the basal-like phenotype.

Topics: Adult; Breast Neoplasms; Carcinoma, Basal Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Phenotype; Tissue Array Analysis; Tumor Suppressor Proteins; Young Adult

Proliferative epithelial breast lesions include a wide variety of benign hyperplastic and noninvasive neoplastic lesions, as well as invasive carcinomas. Mammographically these lesions may show microcalcifications, architectural distortions or mass lesions. The task of the pathologist begins with a preoperative diagnosis by means of minimally invasive biopsy. His diagnosis forms the basis for not only the radiological-pathological correlation diagnosis, but also for the management of benign proliferative breast disease lesions, as well as therapeutic decisions in the case of malignant lesions.In daily practice, immunohistochemistry is the method of choice for clarifying difficult cases. The aim of this chapter is to describe the relevant markers in breast pathology and to provide an algorithmic approach to different proliferative breast disease lesions.

Topics: Biomarkers; Biopsy; Breast Diseases; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Diagnosis, Differential; Epithelium; Female; Fibrocystic Breast Disease; Humans; Hyperplasia; Immunohistochemistry; Keratins

Dense inflammation can obscure nonmelanoma skin cancer (NMSC) on frozen sections, prompting removal of additional layers to ensure negative margins. Cytokeratin (CK) immunostaining in Mohs micrographic surgery (MMS) has been examined and found to be useful but is limited by lengthy 1-hour processing.. Our objective was to develop an effective ultrarapid CK frozen section immunostain to be used during MMS in cases of NMSC with dense or perineural inflammation.. An ultrarapid immunostain with a mixture of AE1/AE3 monoclonal antibodies was performed in 21 MMS cases and compared with permanent sections prepared from the same material.. The ultrarapid CK protocol stained all of the cells in each of the 21 examples of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in frozen tissue in a way equivalent to immunostains being applied to permanent sections.. The 19-minute CK immunohistochemistry protocol in frozen tissue appears to be as effective at labeling tumor cells of SCC and BCC as methods requiring permanent sections. It is hopeful that this technique may prevent recurrences after MMS and limit the number of Mohs layers required to obtain free margins when inflammation is abundant. It also is effective in uncovering subtle perineural invasion.

Topics: Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Frozen Sections; Humans; Immunohistochemistry; Keratins; Male; Mohs Surgery; Skin Neoplasms; Staining and Labeling; Time Factors

A case of distinctive benign follicular neoplasm previously reported under the designation of trichogerminoma is described. A 45-year-old man presented with an asymptomatic nodule on the scalp since 3 years. Histologically, the lesion corresponded to a well-organized, symmetrical dermal nodule made up of basophilic lobules included in a fibrocytic stroma. The lesion had the characteristics of hair germ tumors; however, most lobules depicted a distinctive pattern of rounded nests of concentrically arranged clear cells. Small follicle bulb-like basophilic structures, foci of sebaceous differentiation, and areas of infundibulocystic, isthmic, and outer sheath keratinization were also seen. This neoplasm and the other tumors with hair germ differentiation such as trichoblastoma and panfolliculoma seem to represent the same spectrum of hair follicle neoplasms only distinguishable by their degree of differentiation.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Diagnosis, Differential; Hair Diseases; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasms, Adnexal and Skin Appendage; Scalp; Skin Neoplasms

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Humans; Keratin-5; Keratins; Male; Membrane Proteins; Neoplasm Recurrence, Local; Prostate; Prostatectomy; Prostatic Neoplasms

Atypical fibroxanthoma (AFX) (dermal pleomorphic sarcoma) remains a somewhat controversial entity. Some authors have averred that AFX is a fiction, suggesting that such lesions merely represent misclassified examples of spindled squamous cell carcinoma. In addition, the immunoperoxidase confirmation of AFX has been less than straightforward and has historically been approached as a diagnosis of exclusion because of the lack of sensitivity and specificity of available "positive" reagents. Procollagen 1 (PC1) and CD10 represent recently developed immunoperoxidase reagents that have been forwarded as useful in this setting, and we sought to characterize our experience, both to confirm the utility of these antibodies and to compare them. Our investigation included 3 separate data sets. Group 1 consisted of a retrospective review of 98 consecutive cases in which PC1 was used in the evaluation of dermatopathology specimens in routine practice during a 13-month interval. Group 2 consisted of a direct comparison of 11 AFX, 11 dermatofibroma (DF), and 7 epithelioid dermatofibroma (EDF) using the CD10 reagent on cases identified by database search. Group 3 consisted of a retrospective review of 47 cases in which CD10 was used in routine practice during a 10-month interval. Group 1 included 47 AFX, 13 carcinomas, and 6 melanomas. PC1 expression was observed in 45 of 47 AFX (96%), with a strong reaction in 78% of cases. Among a comparison group of carcinomas, 13 of 13 displayed strong keratin immunopositivity and 11 of 13 (85%) lacked PC1 expression whereas 2 showed focal weak labeling. Six of six melanomas exhibited avid S100 expression and none labeled with PC1. In group 2, strong CD10 immunoreactivity was present in 11 of 11 AFX. Similarly, 11 of 11 DFs were also positive. In contrast, 6 of 7 cases of EDF lacked CD10 expression. Group 3 included 38 AFX and 9 miscellaneous spindle cell proliferations. Of the 38 AFX, 37 (97%) labeled with CD10 and in 34 (92%) the reaction was strong. PC1 immunostaining was also completed in 34 of 38 AFX from group 3 and 27 (79%) cases showed positive labeling. Our results confirm that both PC1 and CD10 can be used as positive markers of AFX. We believe that CD10 and PC1 immunostaining can be used as a useful adjunct to supplement the diagnosis of AFX, within the context of an immunoperoxidase panel. Not surprisingly, CD10 expression is also common in DF, a benign analog of AFX, with the exception of its epithelioid variant. In direc

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Collagen Type I; Diagnosis, Differential; Epithelioid Cells; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Middle Aged; Neprilysin; Predictive Value of Tests; Procollagen; Reproducibility of Results; Retrospective Studies; S100 Proteins; Sarcoma; Skin Neoplasms; Xanthomatosis

The objective of this study was to determine the predictive impact of several established tumor biological markers and clinicopathological findings for basal-like carcinoma. Expression was determined by immunohistochemistry using antibodies to cytokeratins 5/6, 14, and 17, and the cases were divided into basal-like carcinoma and non basal-like carcinoma. These subgroups were compared in terms of biological markers (HER2, estrogen receptor, progesterone receptor, Ki-67, P-53, and P-glycoprotein) and clinicopathological behavior. Of the 49 basal-like carcinoma cases, 25(51.0%) were P-53-positive, whereas 100 (35.9%) of the 278 non basal-like carcinoma cases were P-53-positive. A high ratio of nuclear Ki-67 expression was detected in 39 (79.6%) of 49 basal-like carcinoma cases and was significantly more common than in non basal-like carcinoma cases (81/278, 29.1%). P-glycoprotein expression was identified in 29 (59.2%) of 49 basal-like carcinomas but only 85 (30.6%) of 278 non basal-like carcinomas. We observed high levels of P-53, Ki-67, and P-glycoprotein, with the reduction or loss of estrogen receptor, progesterone receptor, and HER2 being more obvious, in basal-like carcinomas than in non basal-like carcinomas. Our findings provide further evidence that basal-like carcinoma has different mechanisms of histogenesis.

Topics: Adult; Aged; Aged, 80 and over; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Basal Cell; Carcinoma, Ductal, Breast; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Keratins; Ki-67 Antigen; Middle Aged; Predictive Value of Tests; Receptor, ErbB-2; Receptors, Steroid; Tumor Suppressor Protein p53; Young Adult

The distinction between ocular sebaceous carcinoma, poorly differentiated ocular squamous cell carcinoma and ocular basal cell carcinoma can be challenging. An appropriate immunohistochemical panel may help to differentiate these lesions.. To determine the distribution and use of several immunostains in these specimens, formalin-fixed, paraffin-embedded tissue from several of each was studied using an immunohistochemical technique.. Positive staining for cytokeratin (CK)7 was seen in 100% of sebaceous carcinomas, 77.8% of basal cell carcinomas and 67.7% of squamous cell carcinomas. One hundred percent of sebaceous and basal cell carcinomas were positive for cytokeratin CAM 5.2, while only 83.3% of squamous cell carcinomas were positive. Using epithelial membrane antigen (EMA), 100% of squamous cell carcinomas and 80% of sebaceous carcinomas were positive, while basal cell carcinomas were uniformly negative. One hundred percent of basal cell carcinomas and 80% of sebaceous carcinomas were positive for Ber-EP4, while all squamous cell carcinomas were negative. Finally, 77.8%, 20% and 16.7% of basal cell carcinomas, sebaceous carcinomas and squamous cell carcinomas showed immunoreactivity for the androgen receptor.. An EMA positive, Ber-EP4 positive immunophenotype supports sebaceous carcinoma, EMA positive, Ber-EP4 negative result supports squamous cell carcinoma and an EMA negative, Ber-EP4 positive result supports basal cell carcinoma.

Topics: Adenocarcinoma, Sebaceous; Biomarkers; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Eye Neoplasms; Humans; Immunohistochemistry; Keratin-7; Keratins; Mucin-1; Receptors, Androgen; Sebaceous Gland Neoplasms; Skin

We report a case of a primary lymphoepithelioma-like carcinoma of the skin (LELCS) associated with scar from a previous excision of basal cell carcinoma. The patient was a 68-year-old female with a 3.0 mm skin-colored pearly papule on her forehead that developed over 2-3 months. The patient had a history of a basal cell carcinoma in the same location, which was completely excised 1 year earlier. A biopsy and subsequent excision of the tumor were performed. The tumor consisted of small islands of large pleomorphic mitotically active epithelioid cells surrounded by a very dense lymphoplasmacytic infiltrate. The tumor was associated with dermal scar. There was no connection of tumor with the unremarkable epidermis. Immunohistochemical examination showed that the epithelioid tumor cells were positive for pan-cytokeratin and epithelial membrane antigen, supporting the morphologic impression of LELCS. The lesion was negative for Epstein-Barr virus. Retrospective review of the original excision specimen confirmed the diagnosis of an ordinary basal cell carcinoma. Forty-five cases of LELCS have been reported to date. We report the first case of LELCS to arise in the scar from an excision of a cutaneous malignancy.

Topics: Aged; Biomarkers, Tumor; Carcinoma; Carcinoma, Basal Cell; Cicatrix; Female; Humans; Keratins; Mohs Surgery; Mucin-1; Neoplasms, Second Primary; Skin Neoplasms

Origin of basal cell carcinoma (BCC) is still unclear. We studied the cytokeratin (CK) profile in BCC using monoclonal antibodies against 12 CKs to further investigate the suggested origin of the tumor from follicular matrix cells or from follicular outer root sheath cells and to determine if BCC subtypes can be identified on the basis of their CK profiles. Cases of pilomatricoma and samples of fetal skin served as controls to establish the CK profile in matrical cells and developing follicles during intrauterine life, that of the epidermis and cutaneous adnexa in adult life having been determined in a previous study. The most significant findings were as follows: (a) CK 5 and CK 17 positivity in all the BCCs studied; (b) CK 7, CK 8, CK 18, and CK 19 positivity in 30/52, 33/52, 42/52, and 14/52 BCCs, respectively; (c) CK 14 negativity in almost all the BCCs studied; and (d) lack of CK 1 expression only in 2/2 morpheiform BCCs and 4/10 nodular BCCs. The study suggests a tumorous differentiation toward follicular outer root sheath cells and, in most cases, also toward the glandular components of the pilosebaceous-apocrine unit. No significant difference in the CK profile among the BCC subtypes studied was found.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Fetus; Gestational Age; Hair Diseases; Hair Follicle; Humans; Keratinocytes; Keratins; Pilomatrixoma; Skin; Skin Neoplasms

To clarify the histopathogenesis of Pinkus tumor (fibroepithelial basal cell carcinoma, FEBCC), we have studied cytokeratin (CK) expression in FEBCC using ten different anti-keratin antibodies against CK 1, 7, 8, 10, 14, 15, 16, 17, 18 and 19. Tumor nests consisted of two epithelial components: duct-like structures and basaloid cells of anastomosing strands. In duct-like structure, CK 1, 10, 14, 16, 17 and 19 were detected. CK expression of duct-like structure showed the hyperproliferative state of eccrine intraepidermal ducts. In basaloid cells of anastomosing strands, CK 14 and 17 were detectable. These results suggested that duct-like structure originates from the intraepidermal duct and proliferates to spread in the dermis.

Topics: Aged, 80 and over; Antibodies; Carcinoma, Basal Cell; Eccrine Glands; Eosine Yellowish-(YS); Epithelial Cells; Hematoxylin; Humans; Immunohistochemistry; Keratins; Male; Neoplasms, Fibroepithelial; Skin Neoplasms; Staining and Labeling

To investigate the value of detection of AMACR (P504S), P63 and 34betaE12 cocktail in the early diagnosis of prostate cancer (PCa).. The expressions of AMACR, P63 and 34betaE12 were examined in the biopsy specimens of 42 cases of prostate cancer, 12 cases of high-grade prostatic intraepithelial neoplasia (HGPIN) and 30 cases of benign prostatic hyperplasia (BPH) using the Maxvision single-step immunohistochemical method with triple-antibody cocktail (AMACR/P63/34betaE12) staining and double-color chromogens in single paraffin sections .. The expressions of AMACR, P63 and 34betaE12 were significantly different between PCa and BPH (P < 0.01). The staining of PCa was positive for AMACR and negative for P63 and 34betaE12, and the positivity rate of AMACR was 100%. BPH was strongly expressed for P63 and 34betaE12, but negatively for AMACR. The expression of AMACR was significantly different between HGPIN and BPH (P < 0.01), but not between HGPIN and PCa (P > 0.05), and the positivity rate of AMACR in HGPIN was 91.67%. However, the expressions of P63 and 34betaE12 were significantly different between HGPIN and PCa (P < 0.01), but not between HGPIN and BPH (P > 0.05), and the positivity rate of AMACR in HGPIN was 100%. The level of AMACR expression was not correlated with PCa Gleason score (P > 0.05).. AMACR is a sensitive and specific marker for PCa. P63 and 34betaE12 cocktail staining can increase the sensitivity and specificity of the basal cell detection. The immunohistochemical analysis with triple-antibody cocktail (AMACR/P63/34betaE12) staining and double-color chromogens can improve diagnostic accuracy and has an important applied value for the early diagnosis of prostate cancer.

Topics: Aged; Carcinoma, Basal Cell; Early Diagnosis; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Racemases and Epimerases

The 2004 WHO classification of lung tumours recognised basaloid carcinoma as a variant of squamous and large cell carcinoma. We report a unique case of primary pulmonary adenocarcinoma with a basaloid component. An 82-year-old man underwent pulmonary lobectomy for a 2.8 cm tumour. The patient is disease-free 13 months after diagnosis. Histologically, an invasive carcinoma having a glandular and a solid component was observed. The former was an adenocarcinoma with mucus containing spaces lined by columnar mucinous cells and basaloid cells. The solid component was an organoid proliferation of basaloid-type cells, as in cutaneous basal cell carcinoma. Basaloid cells, but not mucinous cells, were immunoreactive for high molecular weight cytokeratins (CK), CK 7 and, focally, for TTF-1. High Ki67 index, p53 and EGFR expression were also found. This tumour is unique in several respects: (1) The solid areas resemble a conventional basaloid carcinoma, except for the presence of small mucin-containing spaces. (2) The mucinous adenocarcinoma areas contain two layers of columnar and basaloid cells. (3) Both components are neoplastic based on cell morphology, invasive properties and phenotypic profile. These findings indicate that a basaloid variant of adenocarcinoma is also existing in the spectrum of basaloid carcinomas of the lung.

Topics: Adenocarcinoma; Aged, 80 and over; Carcinoma, Basal Cell; Humans; Keratins; Lung Neoplasms; Male; Mucins; Neoplasm Invasiveness; Phenotype; World Health Organization

Gap junctions (GJs) have been shown to play a role in tumor progression including a variety of keratinocyte-derived and non-keratinocyte-derived skin tumors. Here we show that the synthesis of the GJ proteins connexin 26 and connexin 30 (Cx26 and Cx30) is induced in keratinocyte-derived epithelial skin tumors whereas there is either no change or a downregulation of Cx43. Cx26, Cx30, and Cx43 are absent in non-epithelial skin tumors. Further, Cx26 and Cx30 are induced in the epidermis adjacent to malignant melanoma but absent in the epidermis adjacent to benign non-epithelial skin lesions (melanocytic nevi and angioma). The keratinocyte-derived skin tumors are very heterogeneous regarding the Cx26/Cx30 pattern in the epidermis at the periphery of the tumors. We did not observe any difference in the localization of the very similar proteins Cx26 and Cx30 but a variation in intensity of immunoreactivity. As the staining patterns of Cx26 and Cx30 antibodies are not identical to those of CK6, a marker for hyperproliferation, and CK17, a marker for trauma, we discuss that the induction of these gap junctional proteins exceeds a reflection of reactive hyperproliferative or traumatized epidermis. We further discuss the putative roles of these gap junctional proteins in tumor progression.

Topics: Animals; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Connexin 26; Connexin 30; Connexins; Epidermis; Hemangioma; Humans; Keratinocytes; Keratins; Keratosis; Liver; Melanoma; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Nevus, Pigmented; Skin Neoplasms; Warts

A 93-year-old woman developed a mass on her right lower eyelid that was present for more than 6 months but underwent rapid expansion during several weeks prior to her ophthalmological evaluation. Examination revealed an approximately 1.8 cm in diameter, fleshy, fungating growth involving more than 60% of the right lower eyelid. Excisional biopsy disclosed a neoplasm arising from the epidermis composed of adjoining basal cell and signet-ring squamous cell carcinoma, without a transition zone. The cells comprising the basal and squamous cell carcinomas were distinct immunophenotypically, with only the basal cell carcinoma reacting with Ber-EP4 and CAM 5.2 antibodies. To our knowledge, this case represents the first example of a collision tumor composed of basal cell and signet-ring squamous cell carcinoma.

Topics: Aged, 80 and over; Biomarkers; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Signet Ring Cell; Carcinoma, Squamous Cell; Eyelid Neoplasms; Female; Humans; Keratins; Neoplasms, Multiple Primary; Treatment Outcome

Lysyl oxidase initiates the enzymatic stage of collagen and elastin cross-linking. Among five isoforms comprising the lysyl oxidase family, LOX is the better studied. LOX is associated to an antitumor activity in ras-transformed fibroblasts, and its expression is down-regulated in many carcinomas. The aim of this work was to shed light on LOX functions within the epidermis by studying its expression in human basal and squamous cell carcinomas and analyzing the effect of its enzymatic activity inhibition and protein absence on human keratinocytes behavior in a skin equivalent. In both carcinomas, LOX expression by epidermal tumor cells was lacking, while it was up-regulated around invading tumor cells in association with the stromal reaction. Lysyl oxidase activity inhibition using beta-aminoproprionitrile in a skin equivalent model prepared with both primary human keratinocytes and HaCaT cell line affected keratin 10 and filaggrin expression and disorganized the collagen network and the basement membrane. In spite of all these changes, no invasion phenotype was observed. Modelization of the invasive phenotype was only noticed in the skin equivalent developed with LOX antisense HaCaT cell line, where the protein LOX is specifically absent. Our results clearly indicate that lysyl oxidase enzymatic activity is essential not only for the integrity maintenance of the dermis but also for the homeostasis of the epidermis. Moreover, LOX protein plays a role in the skin carcinomas and invasion but not through its enzymatic activity.

Topics: Aminopropionitrile; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cells, Cultured; Collagen; Dermis; Fibroblasts; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratin-10; Keratinocytes; Keratins; Models, Biological; Neoplasm Invasiveness; Phenotype; Protein-Lysine 6-Oxidase; Skin Neoplasms

Topics: Carcinoma, Basal Cell; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-1; Keratin-14; Keratin-7; Keratins

There have been few reports of successful long-term culture of cells established from cutaneous basal cell carcinoma (BCC) tumors. Here, we describe techniques that have enabled us to establish three long-term cultures of BCC cells isolated from BCC tumors that arose in irradiated Patched 1 (Ptch1)(+/-) mice. All three cell lines showed cellular morphology similar to that of BCC tumors and could be propagated for at least 20 passages. In addition, similar to BCC tumors, all cell lines had lost the wildtype Ptch1 allele, expressed BCC molecular markers, and responded similarly to cyclopamine, a small molecule inhibitor of Hedgehog signaling. Finally, we describe an efficient electroporation technique for DNA transfection into the BCC cell lines and show that they have activated Hedgehog signaling activity, albeit at a level lower than that of murine BCCs in vivo. These data indicate that the cell lines are bona fide long-term cultures of BCC cells and that DNA plasmids can be introduced into the BCC cell lines with relatively high transfection efficiency using a modified electroporation technique.

Topics: Animals; Carcinoma, Basal Cell; Cell Culture Techniques; Cell Line, Tumor; Electroporation; Keratins; Kruppel-Like Transcription Factors; Mice; Patched Receptors; Patched-1 Receptor; Receptors, Cell Surface; Skin Neoplasms; Transfection; Zinc Finger Protein GLI1

A spindle cell carcinoma arose three years after the seeming excision of a so-called "infiltrative" basal cell carcinoma (IBCC) in the cheek of an 87-year-old Japanese woman. The patent had no history of irradiation. The tumor was composed of short fascicles and whorling arrangements of spindle to polygonal cells without residual IBCC. Immunohistochemically, the tumor was positive for vimentin, cytokeratin 8 & 18, epithelial membrane antigen, and alpha-smooth muscle actin. Ultrastructurally, the tumor cells had tonofilaments and desmosomes. The patient died after a local recurrence with metastatic lesions in the lung and the neck lymph nodes that were indicated by CT scanning and MRI at nine months after diagnosis. This case and others support the concept that spindle cell carcinoma can pursue an aggressive clinical course.

Topics: Actins; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Carcinoma, Basal Cell; Fatal Outcome; Female; Humans; Keratins; Mucin-1; Neoplasms, Second Primary; Skin Neoplasms; Vimentin

The incidence of skin cancer is increased in transplant recipients. UV radiation, papillomaviruses, and immunosuppression participate in the pathogenesis of these tumors. In addition, donor cells may leave the grafted organ, reach peripheral tissues and either induce immune phenomena or possibly take part in tissue remodeling. Herein, we investigated the possible involvement of donor cells in the development of skin tumors in kidney allograft recipients. We analyzed a series of 48 malignant and benign cutaneous tumors developing in 14 females who had been grafted with a male kidney. The number of male cells was measured on microdissected material by quantitative PCR for Y chromosome. In the samples with high levels of male cells, fluorescent in situ hybridization (FISH) with X and Y probes and/or immuno-FISH with anticytokeratin antibodies were carried out. Male cells were detected in 5/15 squamous cell carcinomas and Bowen disease (range 4-180 copies), 3/5 basal cell carcinomas (91-645), 6/11 actinic keratosis (7-102), 2/4 keratoacanthoma (22-41), and 2/5 benign cutaneous lesions (14-55). In a basal cell carcinoma specimen with a high number of male cells, FISH showed that most cells within the tumoral buds were XY. In this lesion, immuno-FISH showed the presence of XY cytokeratin-positive cells indicating that the tumor nests contained male keratinocytes. In contrast, in other female transplants, male cells present in the tumors were not epithelial. In conclusion, stem cells originating from a grafted kidney may migrate to the skin, differentiate, or fuse as keratinocytes that could, rarely, undergo cancer transformation.

Topics: Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Fusion; Chromosomes, Human, X; Chromosomes, Human, Y; Female; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Karyotyping; Keratinocytes; Keratins; Keratoacanthoma; Keratosis; Kidney Transplantation; Male; Reverse Transcriptase Polymerase Chain Reaction; Skin Diseases; Skin Neoplasms; Stem Cells; Tissue Donors; Transplantation, Homologous

Trichogenic tumors are very rare in genital skin and often cause diagnostic problems because they are mitotically active and they share some histologic features with basal cell carcinomas (BCCs). We present the clinical and histologic features of 16 vulvar trichogenic tumors (6 plaque-like, 10 nodular; average age, 65 years) in comparison with 16 BCCs (11 plaque-like, 5 nodular; average age, 78 years). All trichogenic tumors, except 1 case with HSV infection, were nonulcerated tumors. Superficial plaque-like trichogenic tumors featured basal keratinocyte proliferations with peripheral nuclear palisading but no clefting at the epithelial-stromal interface. Nodular trichogenic tumors consisted of solid lobules of squamous cells and anastomosing cords and reticulations of follicular germinative cells with mitoses and apoptosis. Large pink cells with trichohyaline granules and melanocytes resembling the inner hair sheath, and clear cells resembling the outer root sheath were common. Most cysts were keratinized, but some fluid-filled cysts showed apocrine and sebaceous differentiation. The well-defined mesenchymal component of trichogenic tumors was pale and mucinous, and contained fibrocytes and fibrillary collagen bundles. All BCCs showed surface ulcerations and clefting at the stromal-epithelial interface. BCCs showed no trichogenic differentiation and lacked an organized mesenchymal tumor component. The tumor stroma of BCCs was paucicellular, mucinous, or granulation tissue-like with an inflammatory infiltrate.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasms, Adnexal and Skin Appendage; Skin Neoplasms; Vulvar Neoplasms

Interval breast cancer reduce the effectiveness of mammography screening programs. We studied 95 interval cancers, diagnosed during 1996 to 2001 as part of the population-based Norwegian Breast Cancer Screening Program. These cases were matched on size (+/-2.0 mm) to 95 screen-detected breast cancers, and the tumors were compared by immunohistochemical methods using tissue microarrays. Patients with interval cancers were more likely to be younger [odds ratio (OR), 4.7; P = 0.0001], to have dense breasts (OR, 3.4; P = 0.004), and to have estrogen receptor-negative tumors (OR, 2.6, P = 0.01), and p53 expression was more frequent (OR, 4.0; P = 0.001). Notably, interval cancers were more likely to have a basal epithelial phenotype, in that expression of cytokeratin 5/6 (OR, 2.3; P = 0.04) and P-cadherin (OR, 2.5; P = 0.04) was more frequent in interval cases than in size-matched, screen-detected tumors. In a logistic regression model, p53 expression, age, and breast density were independent predictors of interval cancers. Our data suggest that breast cancers with a basal epithelial phenotype are more likely than nonbasal breast cancers to present between regular mammograms.

Topics: Adult; Age Factors; Aged; Biomarkers, Tumor; Breast; Breast Neoplasms; Cadherins; Carcinoma, Basal Cell; Case-Control Studies; Coloring Agents; Female; Genes, p53; Humans; Immunohistochemistry; Keratins; Logistic Models; Mammography; Mass Screening; Middle Aged; Norway; Oligonucleotide Array Sequence Analysis; Phenotype; Receptors, Estrogen; Risk Factors

Basal cell carcinoma (BCC) is the most common human neoplasm. Much interest lies in determining the genetic basis of BCC to explain the unique locally invasive phenotype and infrequent metastatic behavior of these skin tumors.. We sought to examine a gene expression profile for BCC to elucidate new molecules responsible for its unique growth characteristics.. We analyzed gene expression patterns of 50 BCC tumors using spotted cDNA microarrays of 1718 characterized human genes related to cancer and immunity. This is the largest and most comprehensive gene expression study ever performed for BCC. Nodular and sclerosing histological subtypes of BCC were examined and compared to normal control skin. After statistical filtering, 374 significantly dysregulated genes were sorted by hierarchical clustering to determine trends of gene expression and similarities between patient gene expression profiles.. A total of 165 upregulated genes and 115 downregulated genes were identified. These covered a range of categories, including extracellular matrix, cell junctions, motility, metastasis, oncogenes, tumor suppressors, DNA repair, cell cycle, immune regulation and angiogenesis. Clusters of genes were either commonly dysregulated across the 50 patient sample, or selectively affected in subsets of tumors. Histological subtypes were not distinguishable by hierarchical clustering. Many of the genes elucidated, including collagen type IV subunits and other novel candidates, possess functions related to extracellular matrix remodeling and metastasis.. These results suggest a gene profile which may explain the invasive growth yet rarely metastatic behavior of BCC. The genes identified may also be potential targets for therapeutics aimed at further controlling invasiveness and local destruction of BCC.

Topics: Carcinoma, Basal Cell; Caveolin 1; Caveolins; Collagen; DNA-Binding Proteins; Gene Expression Profiling; Humans; Keratins; Kruppel-Like Transcription Factors; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Phosphoprotein Phosphatases; Skin Neoplasms; Zinc Finger Protein Gli2

Adenoid basal carcinoma (ABC) of the uterine cervix is a rare neoplasm with excellent prognosis. Differential diagnosis between ABC and an ABC-like lesion of adenosquamous cell carcinoma (ASC) of the cervix is important due to their contrasting prognosis. Reported herein are two cases of ABC that have been compared with seven ASC exhibiting ABC-like lesions from approximately 2600 resected uterine cervical malignancies diagnosed at Shikoku Cancer Center. The two ABC were incidentally found in the uterine cervix of 69-year-old and 59-year-old Japanese women due to cervical intraepithelial neoplasia grade 3 and to squamous cell carcinoma, respectively. The ABC consisted of infiltrating nests of basaloid cells with low nuclear atypia. The patients remained alive without recurrence for 9 years and 18 months, respectively. An ABC-like lesion was defined as basaloid cell nests simulating ABC, but with some features indicating malignant potential. However, the differential diagnosis was sometimes difficult because two of seven ABC-like lesions were originally diagnosed as ABC. Immunohistochemically, cytokeratin 7 was negative for the basaloid cells of two ABC, but positive for six of six ABC-like lesions of ASC, while cytokeratin 8 was positive for both ABC and ASC. This cytokeratin pattern might provide a good tool for distinguishing between ABC and an ABC-like lesion of ASC when the histological findings are equivocal.

Topics: Adult; Aged; Carcinoma, Adenoid Cystic; Carcinoma, Adenosquamous; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratin-8; Keratins; Ki-67 Antigen; Middle Aged; Uterine Cervical Neoplasms

Cytokeratins (CKs) are expressed specifically in the cytoplasm of epithelial cells. We investigated the expression of CKs immunohistochemically in basal cell carcinomas (BCCs), epidermis overlying tumour, and skin tumor-associated amyloidosis (STA). Twenty cases of BCC, 11 of which had STA were included to the study. The primary antibodies of CK1-8 (AE3), CK10 (DEK-10), CK14 (LL002), CK17 (E3), CK18 (DC10), CK19 (KS19.1), CK 5/6/18 (LP34), CK8/18 (5D3) were applied to the section immunohistochemically. In BCCs without STA, CK1-8, CK14 and CK17 antibodies were expressed by tumour tissue in all biopsy specimens. In the BCCs with STA, tumour tissue was immunoreactive always with CK1-8 and CK17 antibodies, and commonly immunoreactive with anti-CK 14 antibody. In the epidermis overlying tumour tissue, there was positive immunoreactivity with anti-CK 1-8, CK 5/6/18, CK 10 and CK 14 antibodies in all biopsy specimens. Anti-CK 17 antibody was also positive in 17 biopsy specimens. STA is immunoreactive with anti-CK1-8 in all specimens. There was mild staining with anti-CK5/6/18 and with anti-CK19 whereas no immunoreactivity with anti-CK10 and CK18 antibodies was found. In conclusion, we could not find a significant CK expression difference between BCCs with and without STA. Weak positivity and a few number of CKs were shown in STA when compared with those of BCC and epidermis overlying tumour tissue expressing the more variable CKs. Interestingly, although CKs coexpressed in pairs consisting of one basic and one acidic CK, we detected predominantly basic CKs in STA.

Topics: Amyloidosis; Carcinoma, Basal Cell; Epidermis; Humans; Immunoenzyme Techniques; Keratins; Skin Neoplasms; Stromal Cells

Keratin 19 and nuclear reactivity to an endogenous lectin, galectin-1, represent a potential marker of epidermal stem cells. We detected expression of keratin 19 and nuclear binding sites for galectin-1 in adult cells migrating from the hair follicle, where cells expressing keratin 19 are located in the bulge region. The results were compared with the expression of both markers in cells adhering from suspension prepared from the interfollicular epidermis without keratin-19-positive cells and with nuclear binding sites for galectin-1. The results were compared with data from basal cell carcinomas. All cells were analyzed concerning size, as it is known that cell diameter influences the clonogenic potential of keratinocytes. The major result of this study is the observation of transient expression of keratin 19 and nuclear galectin-1 binding sites in originally negative interfollicular epidermal cells induced by adhesion. These cells were very small in size, similar to basal cells of the interfollicular epidermis or the bulge region of the hair follicle. The influence of the suspension regimen on beta1-integrin expression, cell diameter and growth was also monitored. A population of cells highly positive for beta1 integrin of the same diameter as keratin-19-positive cells insensitive to induction of terminal differentiation by lack of anchorage was characterized. Cells of the same size were also observed in the keratin-19-positive cells of basal cell carcinomas. In conclusion, the expression of poor levels of differentiation induced by cell adhesion is transient. Also, keratin 19 expression should not be exclusively regarded as a marker of stem cell activity.

Topics: Carcinoma, Basal Cell; Cell Adhesion; Cell Culture Techniques; Cell Movement; Cells, Cultured; Epidermal Cells; Epidermis; Galectin 1; Galectin 3; Hair Follicle; Humans; Integrin beta1; Intermediate Filament Proteins; Keratin-10; Keratin-20; Keratinocytes; Keratins; Skin Neoplasms; Time Factors

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-line mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided. The aim of this study was therefore to improve diagnosis by establishing an MBC protein expression profile using immunohistochemistry (IHC) on tissue-microarrays (TMA). Using a series of 779 breast carcinomas ('EC' set), diagnosed initially as MBC, a double-reading session was carried out by several pathologists on all of the histological material to establish the diagnosis as firmly as possible using a 'medullary score'. Only MBCs with high scores, i.e. typical MBC (TMBC) (n=44) and non-TMBC grade III with no or low scores (n=160), were included in the IHC study. To validate the results obtained on this first set, a control series of TMBC (n=17) and non-MBC grade III cases (n=140) ('IPC' set) was studied. The expression of 18 proteins was studied in the 61 TMBCs and 300 grade III cases from the two sets. The global intra-observer concordance of the first reading for the diagnosis of TMBC was 94%, with almost perfect kappa (kappa) of 0.815. TMBC was characterized by a high degree of basal/myoepithelial differentiation. In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R=2.29), MIB1 > 50 (R=3.80), ERBB2 negativity (R=2.24) and p53 positivity (RR=1.45).

Topics: Breast Neoplasms; Cadherins; Carcinoma, Basal Cell; Carcinoma, Medullary; Cell Transformation, Neoplastic; Female; Gene Expression Regulation, Neoplastic; Genes, BRCA1; Genes, erbB-2; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mutation; Neoplasm Proteins; Phenotype; Protein Array Analysis; Tumor Suppressor Protein p53

Two cases of a distinctive variety of basaloid squamous carcinoma (BSC) of the anal canal are described. Both occurred in female patients who presented with bleeding per rectum. Histologic evaluation of the tumors showed lobules and aggregates of medium-sized basaloid cells with distinctive peripheral palisading and focal areas of central, comedo-necrosis. Accompanying dysplasia of the overlying squamous mucosa was absent. However, the microscopic pattern was dominated by the presence of eosinophilic, hyaline, paucicellular basement membrane-like material around and within tumor nests. This appearance together with microcystic spaces simulated that of an adenoid cystic carcinoma. Immunohistochemistry of the tumors revealed the following profile: CK7, CK5/CK6, 34betaE12 positive, CK14 focally positive but CK20 negative. The following were all negative: EMA, CEA, smooth muscle and muscle-specific actin, calponin, and S-100. The tumor cells exhibited diffuse nuclear positivity with p63. The eosinophilic basement membrane hyaline material was positive for collagen type IV and also for laminin. BSC of the anal canal with an adenoid cystic pattern is an infrequently encountered and reported variant, although it is seen more often in the aerodigestive tract. There may be an increased propensity for BSC with an adenoid cystic pattern to metastasize to the liver, but the number of cases encountered are too small to be definitive. The histologic differential diagnosis is true salivary gland-type adenoid cystic carcinoma and basal cell adenocarcinoma. Immunohistochemistry and awareness of this unusual pattern of BSC will facilitate the correct diagnosis being reached.

Topics: Anal Canal; Antibiotics, Antineoplastic; Antigens, CD20; Antimetabolites, Antineoplastic; Antineoplastic Agents; Anus Neoplasms; Biomarkers, Tumor; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Carcinoma, Basosquamous; Cell Nucleus; Cisplatin; DNA-Binding Proteins; Female; Fluorouracil; Follow-Up Studies; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Middle Aged; Mitomycin; Phosphoproteins; Radiotherapy; Time Factors; Trans-Activators; Transcription Factors; Treatment Outcome; Tumor Burden; Tumor Suppressor Proteins; Ultrasonography

In the last decades, a number of clinicopathologic subtypes of squamous cell carcinoma (SCC) of the skin, ranging from highly aggressive tumors with a tendency to recur and metastasize to neoplasms with a favorable prognosis, have been described. SCCs arising from the wall of hair follicles have been briefly mentioned by some authors but never reported in a series.. Cases of SCC arising from the wall of hair follicles were collected from the files of two large German Centers for Dermatopathology and analyzed clinicopathologically and immunohistochemically.. Sixteen cases of SCC developing in hair follicles were found among more than 7000 cases of cutaneous SCC reviewed. In most cases, tumors arose on sun-damaged skin of the face of elderly persons. There was a male predominance (11/5). The most common clinical diagnosis was basal cell carcinoma (BCC). Microscopically, tumors developed in the upper part of hair follicles without or with focal involvement of the overlying epidermis at the border with the involved follicle. Immunohistochemically, tumors were positive for cytokeratin and negative for a battery of immunomarkers, including antibodies against the most common carcinogenic human papillomaviruses (HPV) of the skin. Most tumors were excised by simple excision. In two cases, a recurrence was noted after incomplete excision. No further recurrences or metastasis have been noted after a follow-up period ranging from 11 months to 12 years.. SCC of the hair follicle represents a poorly recognized but distinctive subset of SCC of the skin that should be considered in the differential diagnosis of other cutaneous epithelial tumors. The term follicular SCC (FSCC) is proposed for this neoplasm.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Hair Follicle; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Skin Neoplasms

Topics: Breast Neoplasms; Carcinoma, Basal Cell; Female; Gene Expression Regulation, Neoplastic; Genes, BRCA1; Germ-Line Mutation; Humans; Keratins; Phenotype

Topics: Aged; Biopsy, Fine-Needle; Bronchiectasis; Carcinoma; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Giant Cells; Granuloma; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Nasopharyngeal Neoplasms; Neoplasms, Multiple Primary; Skin Neoplasms

The concept of keratotic BCC is obscure and not well-defined. To elucidate the histopathological and immunohistochemical properties of cornification in BCC and to clarify the concept of keratotic BCC, by careful examination of 600 BCC specimens, we selected 16 cases of BCC that showed cornification. We investigated the precise histopathological features of these 16 cases, and studied the immunohistochemical expression patterns of anticytokeratin (CK) antibodies (CKs 1, 10, 13, 14, 17) and other antibodies in these cornifying (keratotic) BCCs. We compared these data to those from normal adult hair follicles and three types of cornifying cysts (epidermal cyst, tricholemmal cyst and steatocystoma). Six types of cornification were observed in these BCCs; 1) infundibular type (4 cases) with thin laminated corneocytes expressing CKs 1 and 10, 2) tricholemmal (isthmus) type (9 cases) showing compact, homogenous cornified contents with CK 17 expression on the surrounding cells, 3) inner root sheath type (1 case) characterized by compact, blue-gray corneocytes lined by CK 13 positive-squamous cells with red trichohyalin granules, 4) sebaceous duct type (1 case) characterized by crenulated cornified cells expressing CK 17, 5) apocrine acrosyringium type (2 cases) characterized by small duct-like structures lined by eosinophilic cuticle expressing CEA, in association with keratohyaline granules, and 6) cornifying microcyst type (10 cases) characterized by micro and small cystic structures containing the debris of cornified cells, which was associated with the infundibular or tricholemmal type and could be classified as having the primitive features of the tricholemmal type of cornification. The tricholemmal type could be subdivided into two groups: one with keratohyaline granules and the other without keratohyaline granules, and the cornified contents in approximately 30% of the cornified areas in this type were positive for CK 17. The matrical type of cornification (seventh type) was not seen in our study. The examples described as "keratotic BCC" thus far were similar to BCCs with cornification of the tricholemmal (isthmus) or infundibular type. The cornification in BCCs could be classified into seven types. Excluding the cornifying microcyst type, the tricholemmal type is the most common type of cornification. This type will be abnormal and incomplete in attempts to cornify in the form of an isthmus, occasionally with concomitant exhibition of lower infundibular

Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Case-Control Studies; Face; Female; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin Neoplasms

Topics: Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Sebaceous Glands; Skin Neoplasms

Recent genetic investigations support the idea that basal cell carcinoma (BCC) is trichoblastic carcinoma. However, it is generally thought that clear cell basal cell carcinoma is a result of degeneration rather than tricholemmal differentiation.. We report a case of BCC, with clear cell components, that developed within seborrheic keratosis, with histopathological and immunohistochemical findings.. The clear cell components in the present case showed the following four characteristics: (i) at the periphery of the aggregations, columnar clear cells were aligned in a palisade along a well-defined basement membrane; (ii) the nuclei of the columnar clear cells were at the pole opposite the basement membrane; (iii) the clear cells contained glycogen; (iv) in the aggregations with clear cell components, there was diffuse positive staining for cytokeratin 7 (CK7) (OV/TLR/30), but only the inner region stained positive for CK17. These four characteristics are comparable to those of the lower portion of normal outer root sheath. In addition, the BCC in the present case was partly composed of squamous cells that contained glycogen and were selectively positive for CK17 - features similar to those of squamous cells in normal outer root sheath.. Some clear cell BCCs are simply the result of degenerative change, but other clear cell BCCs may be the result of tricholemmal (at the lower portion) differentiation.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Hair Diseases; Hair Follicle; Humans; Immunoenzyme Techniques; Keratin-7; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Skin Neoplasms

Mohs micrographic surgery (MMS) is a technique that offers excellent cure rates in the treatment of basal cell carcinoma (BCC). One of the reasons for its success is the 100% visualization of the resection margins. Still, recurrences do occur in 2% to 5% of the treated BCCs. It has been suggested that BCC cells in frozen sections stained with hematoxylin and eosin (H&E) may be missed.. To determine whether an additional immunohistochemical staining with a cytokeratin marker (MNF 116) indicates BCC cells in sections in which the H&E-stained frozen sections were negative.. The Mohs procedure was performed under standard conditions in which H&E-stained slides were judged by the Mohs surgeon and the pathologist. After the H&E slides where judged negative, an extra slide was stained using immunohistochemistry and a monoclonal antibody against cytokeratin (MNF 116).. A total of 143 complete slides were stained and judged by two Mohs surgeons and a pathologist. One of the 143 slides stained with MNF 116 showed positive staining where the H&E slides were negative, which is 0.7% of the slides. However, this single slide represents a failure of nearly 2% of the treated patients.. Frozen sections stained with H&E in MMS offer enough security in detecting BCC cells during surgery; however, adjuvant cytokeratin staining can be useful in very selected cases of aggressive growing BCC.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma, Basal Cell; Coloring Agents; Eosine Yellowish-(YS); Frozen Sections; Hematoxylin; Humans; Immunohistochemistry; Keratins; Middle Aged; Mohs Surgery; Skin Neoplasms

Gain-of-function mutations in SMO have been implicated in constitutive activation of the hedgehog signaling pathway in human basal cell carcinomas (BCCs). We used a truncated keratin 5 (DeltaK5) promoter to assess the potential role of the human M2SMO mutant in BCC development in adult transgenic mice. DeltaK5-M2SMO mouse epidermis is hyperproliferative, ex presses BCC protein markers and gives rise to numerous epithelial downgrowths invading the underlying dermis. Lesions strikingly similar to human basaloid follicular hamartomas develop, but BCCs do not arise even in elderly mice. Hedgehog target gene transcripts were only modestly upregulated in mouse and human follicular hamartomas, in contrast to the high levels detected in BCCs. Cyclins D1 and D2 were selectively upregulated in mouse BCCs. Our data suggest that the levels of hedgehog pathway activation and G(1) cyclins are major determinants of tumor phenotype in skin, and strongly implicate deregulated hedgehog signaling in the genesis of human basaloid follicular hamartomas. Expression of an activated SMO mutant in keratinocytes appears to be insufficient for the development and/or maintenance of full-blown BCCs.

Topics: Alopecia; Animals; Carcinoma, Basal Cell; Cell Differentiation; Hamartoma; Hedgehog Proteins; Humans; Hyperplasia; Keratin-15; Keratin-5; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Phenotype; Promoter Regions, Genetic; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Signal Transduction; Skin Neoplasms; Smoothened Receptor; Trans-Activators

The histogenesis of trichilemmoma remains unclear.. To clarify the histogenesis of trichilemmoma by evaluating its cytokeratin (CK) expression.. In three cases of trichilemmoma, CK expression was studied immunohistochemically using seven antikeratin antibodies against CK1, 10, 14-17 and 19, respectively.. CK1 and CK10 were present in keratinizing ductal epithelium. CK14 was present in the whole layer. CK15 was present in suprabasal layers in two cases. CK16 was present in the suprabasal layer, but was absent in keratinizing ductal epithelium. CK17 was present in suprabasal layers and the sebaceous duct-like structure. CK19 was totally absent.. These results showed that trichilemmoma may differentiate mainly towards two directions: infundibular keratinization and proliferation of the outer root sheath with undifferentiated and pluripotent characteristics.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Cell Differentiation; Female; Hair Diseases; Hair Follicle; Humans; Keratins; Middle Aged; Neoplasm Proteins; Skin Neoplasms

A basal epithelial phenotype is found in not more than 15% of all invasive breast cancers. Microarray studies have shown that this phenotype is associated with breast cancers that express neither estrogen receptor (ER) nor erbB-2 (HER2/neu) (i.e., ER/erbB-2-negative tumors). The ER/erbB-2- negative phenotype is also found in breast cancers occurring in BRCA1 mutation carriers (i.e., BRCA1-related breast cancers). We tested the hypothesis that BRCA1-related breast cancers are more likely than non-BRCA1/ 2-related breast cancer to express a basal epithelial phenotype. Among 292 breast cancer specimens previously analyzed for ER, erbB-2, p53, and germline mutations in BRCA1 and BRCA2, we identified 76 that did not overexpress ER or erbB-2. Of the 72 specimens with sufficient material for testing, 40 expressed stratified epithelial cytokeratin 5 and/or 6 (5/6). In univariate analysis, the expression of cytokeratin 5/6 was statistically significantly associated with BRCA1-related breast cancers (odds ratio = 9.0, 95% confidence interval = 1.9 to 43; P =.002, two-sided Fisher's exact test). Thus, germline BRCA1 mutations appear to be associated with a distinctive breast cancer phenotype.

Topics: Breast Neoplasms; Carcinoma, Basal Cell; Female; Genes, BRCA1; Germ-Line Mutation; Heterozygote; Humans; Keratins; Phenotype

The Sonic Hedgehog (Shh) signalling pathway plays a central role in the development of the skin and hair follicle and is a major determinant of skin tumorigenesis, most notably of basal cell carcinoma (BCC). Various mouse models involving either ablation or overexpression of key members of the Shh signalling pathway display a range of skin tumours. To further examine the role of Shh in skin development, we have overexpressed Shh in a subset of interfollicular basal cells from 12.5 dpc under the control of the human keratin 1 (HK1) promoter. The HK1-Shh transgenic mice display a range of skin anomalies, including highly pigmented inguinal lesions and regions of alopecia. The most striking hair follicle phenotype is a suppression in embryonic follicle development between 14.0 and 19.0 dpc, resulting in a complete absence of guard, awl, and auchene hair fibres. These data indicate that alternative signals are responsible for the development of different hair follicles and point to a major role of Shh signalling in the morphogenesis of guard, awl, and auchene hair fibres. Through a comparison with other mouse models, the characteristics of the HK1-Shh transgenic mice suggest that the precise timing and site of Shh expression are key in dictating the resultant skin and tumour phenotype.

Topics: Animals; beta Catenin; Carcinoma, Basal Cell; Cell Division; Cytoskeletal Proteins; Hair Follicle; Hedgehog Proteins; Homeostasis; Keratins; Mice; Mice, Transgenic; Morphogenesis; Skin Neoplasms; Trans-Activators

A nodule arising within the nevus sebaceus on the vertex of the scalp of a 68-year-old woman was histopathologically and immunohistochemically investigated. We also used immunohistochemistry to investigate the cytokeratin (CK) distribution of the outer root sheaths of normal terminal hair follicles. The nodule consisted of two parts, a main exophytic part with a lobular proliferation and a small peripheral part with the features of trichoblastoma. The main exophytic lesion consisted of lobular aggregations composed of both or either basaloid cells and clear cells with the silhouette and cytology of malignancy. The columnar clear cells were aligned in a palisade at the periphery of the aggregations of clear cells, and the aggregations located in the superficial dermis were connected to the follicular infundibular structures. Almost all of the neoplastic aggregations were diffusely positive for CK7 (OV/TLR/30), and the innermost or inner cells of the neoplastic aggregations were positive for CK17; a similar staining pattern to that in the lower portion of the outer root sheath between the A and B fringes in normal terminal hair follicles. The exophytic part of the lesion was a malignant neoplasm with differentiation mainly toward the lower segment of the outer sheath between the A and B fringes of the terminal hair follicle, namely tricholemmal carcinoma. Our case may represent a collision of two distinctive neoplasms (tricholemmal carcinoma and trichoblastoma), however, an intimate relationship between these two neoplasms also should be considered.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Female; Hair Follicle; Hamartoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasms, Second Primary; Nevus; Scalp; Sebaceous Gland Neoplasms; Skin Diseases; Skin Neoplasms

The squamous stratified epithelia contain a proliferative (harboring mitotic activity) and a differentiating compartment. Due to the potential of protein-carbohydrate interactions to regulate cellular activities we introduced a mammalian lectin to cyto- and histochemical analysis. We answer the questions of whether and to what extent this new probe can pinpoint differentiation-dependent glycosylation changes in sections and in culture of keratinocytes.. Purification and labeling enabled monitoring of galectin-3 reactivity in frozen sections of human and pig epidermis and basal cell carcinomas as well as in culture of keratinocytes. The staining pattern of the lectin was correlated with the staining profile of other cell markers including desmosomal proteins, beta(1) integrin, and the proliferation marker Ki-67. The Dolichos biflorus agglutinin (DBA) sharing binding reactivity of galectin-3 to the A type histoblood group epitope was used for comparison.. Both lectins exhibit suprabasal binding. However, their profiles were not identical, substantiated by lack of coinhibition. Strong DBA reactivity was also observed in a limited number of basal layer cells, namely in cells without the expression of the proliferation marker Ki-67. Cultured mitotic epidermal cells have no reactivity for DBA. Presence of ligands for this plant lectin was connected with decreased positivity of nuclei for Ki-67 and the occurrence of ring-shaped nucleoli, micronucleoli or absence of nucleoli. Considering colocalization the pattern of galectin-3-binding sites coincided with the presence of desmosomal proteins such as desmoplakin-1 and desmoglein but not beta(1) integrin, a potential ligand. Interestingly, studied basal cell carcinomas expressed no binding sites for galectin-3, while a limited number of cells were DBA-reactive.. The expression of galectin-3-binding sites and also DBA-reactive glycoligands correlates with an increased level of differentiation and/or cessation of proliferation in the examined squamous stratified epithelia. Further application of tissue lectins for characterizing ligand expression and its modulation is an important step to reveal functional relevance.

Topics: Animals; Binding Sites; Carcinoma, Basal Cell; Cell Differentiation; Cells, Cultured; Cytoskeletal Proteins; Desmogleins; Desmoplakins; Epithelial Cells; Epithelium; Galectin 3; Glycosylation; Humans; Immunohistochemistry; Integrin beta1; Keratinocytes; Keratins; Ki-67 Antigen; Mice; Plant Lectins; Protein Binding; Skin Neoplasms; Swine

Several reports have documented the coexistence of basal cell carcinoma (BCC) with other lesions, including melanoma. This study was performed to determine whether nests of BCC contain benign melanocytes and Langerhans [corrected] cells. Ten cases of BCC were investigated to determine whether benign melanocytes and Langerhans [corrected] cells populate tumor nests. The BCCs were stained with antibodies to cytokeratin AEI/AE3, S-100, HMB-45, Melan-A, and CD1a proteins. We report that all 10 BCCs were populated by dendritic melanocytes distributed at the periphery (5/10 cases) or evenly throughout tumor nests (5/10 cases). Clusters of melanocytes were not identified in any of the BCCs. A total of 9 of 10 tumors showed staining of dendritic Langerhans cells with CD1a. A total of 8 of 10 tumors stained with cytokeratin AEI/AE3; in 6 of the 8 tumors, the staining was focal. We compared these findings with a single example of a BCC and melanoma in situ (MIS) collision tumor in which the cytokeratin AE1/AE3-positive epithelial nests of BCC were populated by a high density of malignant melanocytes that stained with S-100 and HMB-45. Melanocytes were disposed singly and in clusters of two or more cells within BCC tumor nests. We conclude from this study that BCCs are regularly populated by benign melanocytes and Langerhans [corrected] cells. Furthermore, when BCC is infiltrated with malignant melanocytes of MIS, the melanocyte density is higher and clusters of melanocytes can be observed. The significance of these two findings is unclear, as additional cases of BCC MIS collision tumor need to be studied.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Basal Cell; Humans; Immunoenzyme Techniques; Keratins; Langerhans Cells; Melanocytes; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins; Neoplasms, Multiple Primary; S100 Proteins; Skin Neoplasms

Epidermal changes overlying dermatofibromas (DFs) have been described as ranging from psoriasiform simple hyperplasia to basaloid hyperplasia sometimes morphologically indistinguishable from superficial basal cell carcinoma (BCC). To characterize epidermal hyperplasia overlying DFs and to determine its association with the disease process, we examined 30 cases of DF showing hyperplastic epidermis. We used nine immunohistochemical markers associated with keratinocyte proliferation or differentiation. In DFs, the dermal metallothionein (MT) expression and immunophenotypic changes with regard to epidermal differentiation varied depending on the stage of lesional evolution of the DFs. Immunostaining for epidermal growth factor receptor (EGFR), MT, and keratin 6 (K6) increased in simple hyperplastic epidermis (SHE) overlying DFs (n = 11), whereas it gradually diminished in basaloid hyperplastic epidermis (BHE) overlying DFs (n = 19). In SHE, there was a significant increase in K14 expression. Among 19 BHE cases, 12 showed premature expression of involucrin and delayed appearance of K1 along with aberrant expression of K14. Conversely, the remaining 7 BHE cases showed a pattern of involucrin and K1 similar to that of normal skin coinciding with decreased or absent dermal MT expression. Loricrin and filaggrin expression in all DFs was the same as that of normal skin. Based on the sparse positivity of Ki-67 in the hyperplastic epidermis overlying DFs, we found that the biologic ability of BHE and SHE was not apparent in the hyperproliferative state observed in psoriasis and BCC. These results suggest that the dermal fibrohistiocytic process may trigger the induction of SHE overlying DFs by an unknown mechanism and then mediate both the abnormal keratinocyte differentiation and the transformation of SHE to BHE through the evolution of the dermal lesions.

Topics: Biomarkers; Carcinoma, Basal Cell; Cell Differentiation; Cell Division; Epidermis; ErbB Receptors; Filaggrin Proteins; Histiocytoma, Benign Fibrous; Humans; Hyperplasia; Immunoenzyme Techniques; Keratinocytes; Keratins; Metallothionein; Precancerous Conditions; Psoriasis; Skin Neoplasms

Hair keratins are specifically expressed in hair and nails. We previously demonstrated the expression of hair keratin basic 1 mRNA in pilomatrixomas. We recently developed a method for immunohistochemical staining of the group of acidic keratins, which have not yet been investigated in human tumours.. To study the expression of eight members of the type I hair keratin subfamily in pilomatrixomas and other skin tumours of follicular origin.. We performed immunohistochemistry on paraffin sections of formalin-fixed pilomatrixomas (40), trichoepitheliomas (10), trichoblastomas (10), desmoplastic trichoepitheliomas (10) and basal cell carcinomas (10), using antibodies against type I hair keratins hHa1, hHa2, hHa3-II, hHa4, hHa5, hHa6, hHa7 and hHa8 as well as cytokeratin CK17.. While CK17 was found in almost all tumours investigated, hair keratins were exclusively expressed in pilomatrixomas. Their expression was restricted to areas of transitional cells, located between outer basophilic matricial cells and an inner zone of eosinophilic shadow cells. The most frequently and most strongly expressed hair keratins were hHa1, hHa2, hHa5 and hHa8, whereas hHa4 and hHa6 were only weakly expressed. No positive staining was observed with anti-hHa3-II and anti-hHa7 antibodies. Hair keratin expression in intermediate maturation stage pilomatrixomas resembled that of normal hair follicles, with early matricial and cuticular keratins hHa5 and hHa2 being expressed in lower transitional cells, followed by expression of early cortex keratins hHa1 and hHa8 in intermediate transitional cells and the late cortex keratins hHa4 and hHa6 in upper transitional cells. The latter were, however, seen only in a few intermediate maturation stage pilomatrixomas and were generally absent in late-stage pilomatrixomas.. These changes in hair keratin expression patterns indicate that the maturation of pilomatrixomas towards large areas of shadow cells is associated with a gradual loss of differentiation-specific hair keratins. The complex hair keratin expression in pilomatrixomas is a further argument in favour of a hair matrix origin of this tumour.

Topics: Carcinoma, Basal Cell; Hair Diseases; Hair Follicle; Humans; Keratins; Neoplasm Proteins; Neoplasms, Basal Cell; Pilomatrixoma; Skin Neoplasms

2-18% of ductal carcinoma-No Special Type (NST) are reported to express basal cell keratin 14 and such tumours may have a different metastatic pattern and prognosis. We performed immunohistochemistry for cytokeratins 19 (luminal) and 14 (basal) on 92 ductal carcinoma-NST. Those tumours showing CK14 expression were further characterized by immunohistochemistry for myoepithelial cell phenotype and analysed by comparative genomic hybridization. The 7 cases of ductal carcinoma-NST exhibiting a basal cell phenotype were all grade III tumours and showed a molecular cytogenetic profile similar to more conventional myoepithelial cell carcinomas. Therefore it appears that grade III invasive ductal carcinomas contain a subset of tumours with specific morphological and cytogenetic characteristics, and probably prognosis for the patient.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Basal Cell; Carcinoma, Ductal, Breast; Cell Differentiation; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Myoepithelioma; Neoplasm Proteins; Neoplasm Staging; Nucleic Acid Hybridization; Prognosis

To explore the biological features of basaloid squamous cell carcinoma (BSC) of the esophagus.. Cytokeratins (CK4, CK18 and CK19), epithelial membrane antigen (EMA), carcino embryo antigen (CEA), alpha-smooth muscle antigen (alpha-SMA), S-100, laminin (LN), collagen IV (Col-IV), neural-specific enolase (NSE), proliferating cell nuclear antigen (PCNA) and p53 antibodies were used to detect the corresponding antigen expression in 8 cases of BSC with ABC immunohistochemical methods.. Two kinds of BSC cell components have different responses to the above antibodies. For basaloid cells (BCs), 7 cases were positive for CK19, and were negative for the other 4 epithelial antibodies CK4, CK18, CEA and EMA. BCs of 4 cases were positive to the muscular antibodies alpha-SMA and S-100, and the hyaline degeneration in the tumor nests was positive for LN and Col-IV. BCs had a high index of PCNA, with an average level of 54%. For squamous cells (SCs), 7 cases were positive for the epithelial antigen CK4, CEA and EMA, but were negative for CK19, alpha-SMA and S-100. The index of PCNA of SC was low, with an average level of 25%.. BSC of the esophagus is a high-malignancy tumor which is of multi-oriented differentiation. BCs represent basal cells which have the tendency of myoepithelial differentiation and have strong proliferation ability, whereas SCs represent typical squamous cell differentiation.

Topics: Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Mucin-1; Proliferating Cell Nuclear Antigen; S100 Proteins

Trichoblastoma(s) (TB) are benign neoplasms of follicular differentiation frequently found in nevus sebaceus. Many morphologic features are shared with nodular basal cell carcinoma(s) (BCC), sometimes rendering the differential diagnosis difficult. Because both neoplasms can simulate components of mature hair follicles histologically, we attempted to corroborate this by immunohistochemical examination of cytokeratins and hair keratins differentially expressed in the hair follicle. Trichoblastoma(s) and BCC showed homogenous expression of CK14 and CK17. The innermost cells of the tumor nodules in all TB and in 72% of BCC were positive for CK6hf. Using a specific CK15 antibody, 38% of TB showed a focal labeling and all BCC remained negative; 70% of TB and 22% of BCC expressed CK19. CK8 was expressed by numerous Merkel cells present in all TB but in none of the BCC examined. All type I and II hair keratins tested, (especially hHa1, hHa5, and hHa8) remained negative in all tumors examined. Trichoblastoma(s) and BCC show consistent expression of CK6hf, CK14, and CK17; variable expression of CK15 and CK19; and absence of hair keratins. This indicates a differentiation toward the outer root sheath epithelium or the companion layer and not toward the inner root sheath, matrix, or cortex.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Diagnosis, Differential; Hair; Humans; Immunohistochemistry; Keratins; Skin; Skin Neoplasms

Topics: Animals; Carcinoma, Basal Cell; Cattle; Cell Transformation, Neoplastic; Epidermis; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Hedgehog Proteins; Keratinocytes; Keratins; Kruppel-Like Transcription Factors; Mice; Mice, Transgenic; Neoplasm Proteins; Neoplasms, Multiple Primary; Promoter Regions, Genetic; Proteins; RNA, Messenger; RNA, Neoplasm; Signal Transduction; Skin Neoplasms; Trans-Activators; Transcription Factors; Zinc Finger Protein Gli2

The reactions of a number of epithelial skin tumours in dogs to a panel of monoclonal antibodies against different human cytokeratins (CKs) were examined immunohistochemically, the purpose being to detect a specific CK profile. CK 6 was present in all epithelial skin tumours with the exception of pilomatrixoma. CK 14 was found in basal cell-derived neoplasias and in sebaceous and perianal gland tumours. CK 10/11 was restricted to spinous cell-derived tumours and CK 8/18 was limited to sweat gland tumours.

Topics: Animals; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Humans; Immunohistochemistry; Keratins; Skin; Skin Neoplasms

Seventy-five skin tumours were studied to investigate the value of immunohistochemistry in differentiating basal cell, squamous cell and basosquamous carcinomas of the skin.. Archived paraffin-embedded tissue samples of basal cell carcinomas (n = 39), squamous cell carcinomas (n = 23) and basosquamous carcinomas (n = 13) were stained immunohistochemically using a panel of antibodies. All of the basal cell carcinomas stained positively for Ber EP4, in contrast to the group of squamous cell carcinomas, that showed no staining. Basosquamous carcinomas all showed at least some areas of Ber EP4 positivity. None of the basal cell carcinomas, but most of the squamous cell carcinomas (22 of 23) expressed epithelial membrane antigen (EMA). Only one of the basosquamous carcinomas expressed EMA positivity focally. CAM 5.2, carcinoembryonic antigen (CEA) and 34betaE12 antibodies lacked specificity in relation to the different tumour types.. Distinction of basal and squamous cell carcinomas of the skin can be readily achieved with routine immunohistochemistry using Ber EP4 and EMA. Identification of basosquamous carcinoma is also facilitated with this method.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Surface; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Skin Neoplasms

Classical trichoblastic fibroma or small nodular type trichoblastoma (Ackerman) is a rare tumour. This tumour, trichoepithelioma and basal cell carcinoma (BCC) have some overlapping histopathological features. There are only a few reports on immunohistochemical studies in large series of these three neoplasms. We investigated immunostaining patterns of 10 different anticytokeratin (CK) antibodies and several other markers in these neoplasms, comparing them with the patterns in normal adult and fetal skin. In trichoblastic fibroma (three cases), CK1/5/10/14, CK7, CK8/18, CK10/11, CK14, CK17 and CK19 were expressed in the basaloid nests, and CK6 and involucrin were detected in the inner layers of keratinous cysts. Trichoepithelioma (seven cases) expressed CK1/5/10/14, CK8/18, CK14, CK17 and CK19 in the basaloid nests, and CK6, CK10, CK10/11 and involucrin were positive in the keratinous cysts. However, no CK7 expression was observed. Solid and keratotic types of BCC (29 cases) expressed CK1/5/10/14, CK7, CK8/18, CK14, CK17 and CK19 in the basaloid nests. The keratinous cysts in BCC were stained with anti-CK6, CK10, CK10/11 and involucrin antibodies. Coupled with the expression of CK8/18, CK17 and CK19 in the outer root sheath of the adult hair follicle, these three neoplasms shared a keratin phenotype characteristic of the outer root sheath. Judging from our immunohistochemical results, trichoblastic fibroma and BCC cannot be differentiated by their patterns of CK expression. The expression of CK7, which is noted in fetal hair follicles, trichoblastic fibroma and BCC, suggests the presence of subpopulations that retain fetal phenotypic characteristics in these two neoplasms. Although the current concept regards trichoepithelioma and trichoblastic fibroma as a single tumour group, the lack of CK7 expression in trichoepithelioma supports the notion that the two are different.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin; Skin Neoplasms

Trichoepitheliomas and many basal cell carcinomas appear to arise from the hair follicle, and in particular from the hair follicle bulge. This histogenesis is suggested from both morphological and immunohistochemical studies on tumor cells and stroma. Epithelial stem cells are thought to be important in tumorigenesis, and we previously localized a population of stem cells to the bulge area of the outer root sheath. We recently identified an anti-CD8 monoclonal antibody (DAKO clone C8/144B) that cross-reacts with cytokeratin 15 (K15), and serves as a specific marker for the bulge. In this study, we screened a series of trichoepitheliomas (n=13), basal cell carcinomas (n=37) and a variety of other skin tumors with this antibody. All trichoepitheliomas (100%) showed keratin 15 expression, while only a subset of basal cell carcinomas (27%) was K15-positive. Epidermal tumors, including squamous cell carcinomas, were K15-negative. Tumors of follicular derivation such as proliferating trichilemmal cysts were also K15-positive, while others such as pilomatricoma were K15-negative. Expression of K15 in trichoepitheliomas, some basal cell carcinomas and other follicular tumors suggests that these tumors are related to hair follicle stem cells in the bulge.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Basal Cell; Hair Follicle; Humans; Immunoenzyme Techniques; Keratin-15; Keratins; Neoplasms, Basal Cell; Skin Neoplasms; Stem Cells

In the present study, the immunophenotype of basal cell carcinoma was analysed in comparison with human vellus hair follicular keratinocytes. We also established the lectin binding profile of basal cell carcinoma and human vellus hair follicles (VHF), using several lectins with different sugar specificities. Our findings showed an almost identical immunohistochemical profile for basal cell carcinoma and the suprabulbar region of the outer root sheath of VHF, whereas other follicular compartments such as the bulbar, the isthmus or the supraseboglandular regions did not correlate. In particular, homogeneous and constant expression of the basal differentiation markers CK 5 and CK 14 were found in both specimen, with no expression of the simple epithelium type keratin CK 8 and the suprabasal differentiation markers CK 1 and CK 10. CK 19 showed variable expression in basal cell carcinoma, with constant expression in the outer root sheath and the follicular bulge regions, but was always absent in interfollicular epidermal keratinocytes. In addition, the lectin binding profiles of basal cell carcinoma and the outer root sheath in the suprabulbar region of human VHF were comparable, with the presence of binding sites for PNA, Con A and WGA. These findings provide evidence for a histochemical relationship between basal cell carcinoma and the follicular epithelium of VHF which is closer than that with the epidermis, and suggest its possible origin from or possibly its differentiation pattern towards the cells of the outer root sheath and/or the follicular bulge region of the VHF.

Topics: Carcinoma, Basal Cell; Hair Follicle; Histocytochemistry; Humans; Keratinocytes; Keratins; Lectins; Neoplasm Proteins; Skin Neoplasms

Diagnosis of sebaceous carcinoma of the periorbital region is often delayed. Clinically, this lesion can mimic several inflammatory disorders. Histopathologically, it can mimic either squamous cell or basal cell carcinoma.. To identify an immunohistochemical approach to assist in the diagnosis of periorbital sebaceous carcinoma.. The immunohistochemical profiles of several cases of periorbital sebaceous, basal cell, and squamous cell carcinoma were examined.. Although at least focal epithelial membrane antigen (EMA) staining can effectively distinguish sebaceous carcinoma (10 of 11 were positive) from basal cell carcinoma (1 of 16 were positive), most squamous cell carcinomas examined were also focally EMA positive (11 of 14). However, Cam 5.2 reactivity was seen in most sebaceous carcinomas (8 of 11) but no squamous cell carcinomas (0 of 14). In addition, at least focal BRST-1 reactivity was also seen in most sebaceous carcinomas (7 of 11) but no basal cell carcinomas (0 of 16).. Periorbital sebaceous, basal cell, and squamous cell carcinomas have different immunohistochemical staining profiles; a panel of commonly available antibodies, including anti-EMA, BRST-1, and Cam 5.2, may help distinguish these diseases from each other when that distinction cannot be clearly made by light microscopy alone.

Topics: Adenocarcinoma, Sebaceous; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Conjunctival Neoplasms; Diagnosis, Differential; Eyelid Neoplasms; Female; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Mucin-1

Nodular or tumoral melanosis consists of nodular or sheetlike deposits of melanophages in the dermis. When nodular melanosis is present, a completely regressed malignant melanoma is a major diagnostic consideration. We present a case of nodular melanosis due to regression of a pigmented basal cell carcinoma with pilar differentiation. In addition to this case, we present five additional cases of epithelial neoplasms with melanin deposition in the stroma. In each case, the source of the melanin was non-neoplastic dendritic melanocytes intermingled among the tumor cells. Therefore, if nodular melanosis is found, pigmented epithelial neoplasms should also be considered in the differential diagnosis.

Topics: Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Carcinoma, Basal Cell; Humans; Immunohistochemistry; Iron; Keratins; Male; Melanins; Melanoma-Specific Antigens; Melanosis; Middle Aged; Neoplasm Proteins; S100 Proteins; Skin Neoplasms; Vimentin

Recently we demonstrated that the keratin 17 (K17) content exceeded the K16 content in most follicular tumors, in comparison with non-follicular epithelial skin tumours by two-dimensional gel electrophoresis (2-DE), densitometry and immunohistochemistry. At present the origin of basal cell carcinoma (BCC) is unknown. So, based on the above results, we studied keratin expression in eight cases of BCC, in order to analyze tumor differentiation by both biochemical and immunohistochemical methods. Biochemically, using 2-DE and immunoblotting, stratified epithelial keratins K5/K14 and large amounts of K17 were present in all cases. Simple epithelial keratins K8 and K19 were expressed in all and half of the cases, respectively. However, hyperproliferative associated keratins (K6/K16) and keratinized keratins (K1/K10) were detected in only a few cases. Immunohistochemical studies using frozen sections with chain-specific antikeratin monoclonal antibodies against K1, K7, K8, K10, K14, K16, K17, K18 and K19 showed that BCC tumor cells reacted positively with antibodies against K8, K14, K17 and K19, but did not react, or were rarely positive with K1, K7, K10, K16 and K18 antibodies. Predominant expression of K17 and the frequent expression of K8 and K19, with little K6/K16 and K1/K10 expression are the characteristic features of BCC, suggesting that BCC is differentiated towards undifferentiated follicular epithelia, most probably hair bulge cells.

Topics: Aged; Carcinoma, Basal Cell; Electrophoresis, Gel, Two-Dimensional; Female; Humans; Immunoblotting; Immunohistochemistry; Keratins; Male; Middle Aged; Skin Neoplasms

Four mixed Merkel cell and squamous cell carcinomas of the skin are described. The patients ranged in age from 74 to 90 years and demonstrated or had a history of previous ultraviolet or infrared damage to the skin, manifested by basal cell carcinoma, squamous cell carcinoma, actinic keratoses, solar elastosis, and erythema ab igne. Light microscopic examination of all 4 cases revealed invasive neoplasms consisting of 2 distinct but admixed cell types. The predominant cell type was consistent with Merkel cell carcinoma and was characterized by scant cytoplasm, a small dark polygonal nucleus with granular chromatin, a high mitotic rate, and cytokeratin 20 positivity. In each case, the Merkel cell component merged with a cytokeratin 20 negative squamous component characterized by abundant eosinophilic cytoplasm, intercellular bridges, and keratinization with focal squamous pearl formation. Immunohistochemical staining patterns were consistent with the usual pattern for that cell type; transitional cells were not demonstrated. The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from a pluripotent epidermal stem cell.

Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasm; Elastic Tissue; Erythema; Female; Humans; Infrared Rays; Keratins; Keratosis; Male; Mitosis; Neoplasms, Multiple Primary; Skin Aging; Skin Neoplasms; Ultraviolet Rays

Desmosomes are predominant among the types of plaque-bearing adhering junctions found in human skin. These structures contain a set of desmosomal cadherins and cytoplasmic plaque proteins, the synthesis of which is differentiation dependent. As plakophilin 1, a member of the armadillo gene family, is an important accessory desmosomal plaque protein, we raised several monoclonal antibodies specific for this protein and applied immunohistochemical and immunoblotting procedures to study the distribution of plakophilin 1 in desmosomes in adult and fetal skin, psoriatic epidermis, various epithelial skin tumors, and keratinocyte sheets grown in culture. In epidermis, the spinous layers were prominently immunostained by plakophilin 1 antibodies, whereas the basal cell layer was only weakly stained and the stratum corneum was entirely unstained. The staining observed in psoriatic epidermis was somewhat heterogeneous. In hair follicles, the outer root sheath (ORS) was delineated in its suprabasal cell layers, with variable staining in its upper and lower parts. All basal cells of the ORS remained unstained, as did upper inner root sheath (IRS) and matrix cells of lower bulb. In eccrine sweat glands, the reaction was confined to inner dermal ductal cells, with the acini remaining unstained. The desmosomal immunostaining observed in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) was very heterogeneous: In general, junctions in well-differentiated stratified tumor regions were more intensely stained than sections of poorly differentiated and invasively growing BCCs and SCCs. Plakophilin 1 was also prominent in the desmosomes of keratinocyte sheets grown in culture. The cell type-specific, i.e., differentiation-dependent, distribution of desmosomal plakophilin 1 is discussed in relation both to the stratification of the cutaneous epithelia and to tumor differentiation and growth.

Topics: Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Desmosomes; Fetus; Foot; Humans; Immunohistochemistry; Keratinocytes; Keratins; Plakophilins; Proteins; Psoriasis; Skin; Skin Neoplasms

The basosquamous cell carcinoma (BSCC) is a poorly defined and often misunderstood cutaneous malignancy.. The purpose of this study was to compare, using immunohistochemical techniques, the BSCC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC).. BSCC occurring at Pennsylvania State University over the past 10 years were identified. Choosing seven BCC, and nine SCC as controls, all specimens were stained for keratin, lack of apoptosis, glycoproteins, and altered gene products using the avidin/biotin and strep-avidin immunoperoxidase techniques. Each malignancy was then graded for the percentage of cells stained with each marker.. Of the markers studied, all stained to varying degrees the malignant aspects of the specimens. There were similar patterns between tumors, with the BSCC showing a transition zone between typical BCC and SCC. This was most striking for Ber-EP4, where over two-thirds of the BCC stained, none of the SCC, and half of the BSCC showed reactivity.. BSCC has staining patterns similar to both the BCC and SCC. The presence of a transition zone does not support the concept that all BSCC are collision tumors, but rather a differentiation of one tumor into another. We confirm earlier reports that Ber-EP4 could be used to distinguish between classic BCC and SCC. AE1/AE3, bcl-2, TGF-alpha, and p53 were not helpful in separating the tumors.

Topics: Carcinoma, Basal Cell; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; ErbB Receptors; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Proto-Oncogene Proteins c-bcl-2; Skin Neoplasms; Tumor Suppressor Protein p53

Using in situ hybridization, human hair keratin basic 1 (hHb1) gene expression was investigated in human normal scalp. hHb1 transcripts were specifically detected in the cortical cells of hair shaft but neither in the outer and inner root sheaths, nor in the hair cuticle or the medulla. hHb1 expression was detected strongly in cortical cells located from the beginning of the keratogenous zone up to the isthmus. These data specify the localization of hHb1 expression. Furthermore, neoplasms with follicular differentiation, including trichoblastoma, trichoepithelioma, pilomatricoma, pilar carcinoma and basal-cell carcinoma, were analysed for hHb1 gene expression. One of the 4 pilomatricoma specimens examined exhibited a very high level of hHb1 transcripts. Interestingly, this labeling was specifically associated to a transitional cell layer en route to trichocytic differentiation, providing evidence that in pilomatricoma, epithelial germ cells can differentiate towards hair shaft keratinocytes before evolving in ghost cells.

Topics: Carcinoma, Basal Cell; Cell Differentiation; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Hair Diseases; Hair Follicle; Humans; Keratinocytes; Keratins; Neoplasm Proteins; Pilomatrixoma; RNA, Messenger; RNA, Neoplasm; Skin Neoplasms

Trichoblastoma and nodular basal cell carcinoma are generally held to be distinctive epithelial neoplasms with some overlapping features. We investigated 30 trichoblastomas in which the basaloid cells expressed cytokeratins (CK) CK5/6, CK14, CK17, CK19, and, in a few cells, vimentin. The cells of the periphery of small and large cysts showed the same profile. Cells lining the lumen of small cysts expressed CK14, CK17, and involucrin, and those in larger cysts showed a positivity for CK1, CK4, CK10, CK14, CK17, and involucrin. The remaining tested antibodies (CK7, CK8, CK13, CK18, CK20, alpha-smooth-muscle actin) were negative in all cases. The cells of the stroma expressed vimentin and in 22 cases, the CD34 antigen. Seventeen nodular basal cell carcinomas showed exactly the same staining pattern. Furthermore, there are striking immunohistochemical similarities between the neoplastic basaloid cells of both neoplasms and the cells of the hair germ. Therefore, trichoblastoma and nodular basal cell carcinoma cannot be distinguished by their pattern of cytokeratin expression in paraffin sections. The virtually identical cytokeratin pattern seen in trichoblastoma, basal cell carcinoma, and the developing fetal hair follicle is compelling evidence for common differentiation pathway.

Topics: Actins; Adult; Aged; Aged, 80 and over; Antigens, CD34; Carcinoma, Basal Cell; Cell Differentiation; Cysts; Epithelium; Female; Fetus; Gene Expression Regulation, Neoplastic; Hair Follicle; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Melanocytes; Middle Aged; Neoplasms, Basal Cell; Paraffin Embedding; Protein Precursors; Skin Neoplasms; Vimentin

The type and distribution of keratins (K) in malignant tumors of eyelids were examined immunohistochemically to understand the pathomechanism of intercellular interactions. All of the tumor cells in the basal cell carcinoma were positive for K14, which is specific for basal cells, whereas all of them were negative for K10, which is specific for suprabasal layers in stratified squamous epithelia. These findings suggest that basal cell carcinoma may consist of uniform, basal cell-like tumor cells. On the other hand, the squamous cell carcinoma and sebaceous carcinoma, which were positive for either K14 or K10 to varying extent, may consist of various tumor cells with different types and degrees of differentiation. In these tumors, K14 was frequently detected throughout the border cells of the tumor mass. Apoptotic bodies were detected at the region where this continuous distribution of K14 was interrupted. These findings may help to clarify the pathomechanism of the interactions between the tumor cells and stromal cells.

Topics: Adenocarcinoma, Sebaceous; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Eyelid Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged

A case of actinic comedonal plaque is reported. We comment on the case as well as describe the skin surface microscopic features.

Topics: Acne Vulgaris; Aged; Carcinoma, Basal Cell; Diagnosis, Differential; Facial Dermatoses; Humans; Keratins; Male; Photosensitivity Disorders; Skin; Skin Neoplasms

Moderate hyperplasia of Merkel cells (MC) in chronic sun-damaged skin and hypertrophic actinic keratoses is well known. In the present study we investigated the number of MC in 24 samples of chronic radiation dermatitis and 19 cases of fibroepithelioma of Pinkus (FP), which is known to arise preferably in radiation-damaged skin. Using antibodies against the low molecular weight cytokeratins 8, 18, and 20 and chromogranin A to visualize MC, we found hyperplasia of MC in chronic radiation dermatitis. Additionally, in all FPs we could detect many MC, especially in areas with a pronounced fenestrated pattern. Recently, regulative functions of MC on the growth of follicular epithelium under various conditions were discussed. Thus, MC hyperplasia suggests a causal role also in the development of FP. In this context, hyperplasia of MC in chronic radiation dermatitis could explain the frequent occurrence of FP due to radiation exposure. As we recently found MC also in trichoblastomas but not in basal-cell carcinomas, the MC in FP may indicate its relationship to the benign trichoblastoma rather than to the basal-cell carcinoma. It is possible that regulative influences of the MC are important for the clinically rather benign course of FP.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Chromogranin A; Chromogranins; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Merkel Cells; Radiodermatitis; Skin Neoplasms

The increased glucose uptake seen in cancer cells correlates with the expression of human erythrocyte glucose transporter (Glut1) protein in certain human malignancies.. Our purpose was to determine Glut1 expression in cutaneous neoplasms.. A polyclonal anti-Glut1 antibody (MYM) and a standard ABC immunoperoxidase technique were used to determine Glut1 expression in invasive squamous cell carcinomas (SCCs), SCC in situ, basal cell carcinomas (BCCs), melanomas, actinic keratoses (AKs), seborrheic keratoses, common acquired nevi, and scars with regenerative epidermal hyperplasia.. All of the cases of SCC in situ, 14 of 15 (93%) of the SCC, and 13 of 15 AKs (87%) showed intense membranous staining for Glut1. Glut1 staining was present in the epidermis of 8 of 15 scars (53%) but was not detected in any BCC, even in areas of focal keratinization and squamous metaplasia. Glut1 reactivity was absent in the melanomas and seborrheic keratoses.. Glut1 expression in a cutaneous lesion strongly suggests a proliferative lesion of the squamous cell type.

Topics: Antibodies; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Division; Cicatrix; Dermatitis, Seborrheic; Epidermis; Epithelial Cells; Gene Expression Regulation, Neoplastic; Glucose; Glucose Transporter Type 1; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Keratosis; Melanoma; Monosaccharide Transport Proteins; Neoplasm Invasiveness; Nevus; Regeneration; Skin Neoplasms

We investigated cell proliferation and expression of cytoskeletal proteins in 32 cases of primary basal cell carcinomas (BCC), 10 cases of recurrent BCC, and 10 cases of metatypical carcinomas (MTC). Paraffin-embedded biopsies were evaluated immunohistochemically with a battery of antibodies. Antibodies to proliferating cell nuclear antigen (PCNA) demonstrated comparatively low numbers of proliferating cells in 25 of 32 cases of primary BCC. In contrast, both recurrent BCC and MTC exhibited three to four times higher levels of proliferating cells than primary BCC. PCNA-positive cells were usually distributed uniformly throughout the lobules; at times, however, they were localized to the outer areas of those neoplasms, with a comparatively low level of proliferation index. Antibodies to keratin 17 strongly stained cells of all BCC cases, and antibodies to keratin 8 reacted with most of them. In contrast, the staining intensity of both types of keratin in MTC was decreased six to eight times as compared with all BCC. In addition, cells of eight BCC and three MTC reacted with antibodies to smooth muscle alpha-actin and myosin, neoplasms that did not differ by the number of PCNA-positive nuclei from carcinomas without contractile proteins. The differences in cell proliferation and keratin expression between BCC and MTC may be useful criteria for further distinguishing these carcinomas. The appearance of contractile proteins in some BCC and MTC may be the result of, or implies, myoepithelial differentiation.

Topics: Actins; Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Basosquamous; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myosins; Neoplasm Recurrence, Local; Skin Neoplasms

Benign cutaneous adnexal tumors displaying divergent differentiation are rare, with very few well-documented cases reported in the literature. We describe eight cases of benign adnexal tumors showing a variable combination of eccrine, apocrine, and folliculosebaceous differentiation. Clinically, all tumors presented as solitary, slowly enlarging dermal or subcutaneous nodules located in the head and neck and the extremities. Histologically, they were characterized by well-circumscribed, unencapsulated nodules composed of a lobular proliferation of epithelial cells displaying a spectrum of trichogenic, sebaceous, apocrine, and eccrine differentiation. The histological spectrum included lobules and trabeculae of basaloid cells with glandular and ductal elements, well-formed folliculosebaceous units, primitive follicles, and foci of tricholemmal keratinization. Immunohistochemical evaluation in four cases showed similar cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen staining profiles as those reported for sweat gland adenomas; in addition, focal S-100 protein positivity and GCDFP-15 positivity could also be demonstrated, suggesting eccrine-apocrine differentiation. The tumors were most frequently confused histologically with other adnexal neoplasms, including sebaceoma, sebaceous adenoma, basal cell carcinoma, chondroid syringoma, and trichoepithelioma. The present series highlights the capability.

Topics: Adenoma; Adenoma, Pleomorphic; Adenoma, Sweat Gland; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carrier Proteins; Eccrine Glands; Epithelium; Female; Glycoproteins; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Membrane Transport Proteins; Middle Aged; Mucin-1; Neoplasm Proteins; Neoplasms, Basal Cell; S100 Proteins; Sebaceous Gland Neoplasms; Sweat Gland Neoplasms

Immunohistochemical detection of certain low to intermediate molecular weight keratins often is impaired in routinely processed specimens due to masking of these antigens by formalin fixation. Despite standard enzymatic digestion, AE1:AE3 and CAM 5.2, two of the most currently utilized antikeratin antibody preparations, either stain weakly or fail to stain basal keratinocytes and tumors composed of basaloid keratinocytes in paraffin sections of formalin-fixed tissue. We present here our experience with the monoclonal antibody MNF116 which detects keratins 5, 6, 8, 17, and 19 (DAKO, Carpinteria, CA). We have studied 232 routinely-processed skin lesions with MNF116 and compared the staining with that of AE1:AE3 mixture or CAM 5.2. In normal skin, the staining achieved with MNF116 was particularly strong on the basal cells of the epidermis and adnexae. MNF116 was positive in all 154 epithelial tumors and negative in all but one (a leiomyosarcoma) of 78 mesenchymal and melanocytic tumors. AE1:AE3 mixture was positive in all but four poorly-differentiated squamous cell carcinomas and it was only weakly positive in most basal cell carcinomas. CAM 5.2 was positive in tumors of the sweat apparatus, Merkel cell carcinomas, metastatic carcinomas, and 5/15 basal cell carcinomas. We consider that, in routinely processed specimens, MNF116 is very useful and convenient for detection of cytokeratin expression in cutaneous lesions, and therefore helpful in the evaluation of tumors with small cells and other poorly differentiated neoplasms of the skin.

Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Melanoma; Molecular Weight; Paraffin Embedding; Prospective Studies; Retrospective Studies; Skin Diseases; Skin Neoplasms

In this study we developed an in vitro model of nodular basal cell carcinoma (BCC). We obtained pure cultures of BCC cells and compared the morphologic characteristics, ultrastructure, immunophenotype, and behavior of cultured tumor cells with those of their in vivo counterparts. Tumors were excised from patients undergoing Mohs micrographic surgery. We established 69 primary cell cultures from 32 patients with nodular BCC.. Three cell types grew in primary cultures: fibroblasts, normal-appearing keratinocytes, and cells with dual (spindle and epithelioid) morphologic characteristics. Contaminating fibroblasts were removed using 0.125% trypsin-0.02% edetic acid, and normal-appearing keratinocytes were cornified and eliminated by temporarily increasing the concentration of calcium in the growth medium. The cells with dual morphologic characteristics remained intact and exhibited relentless growth in pure cultures. That these seemingly immortal cell strains represent true nodular BCC was demonstrated by (1) their biphasic morphologic characteristics and very slow cell growth rate, (2) their capability for anchorage-independent growth in soft agar, (3) their ultrastructural similarities to freshly excised nodular BCC, (4) their ability to generate antibodies selectively labeling nodular BCC tumor nests in vivo, and (5) their immunophenotypic similarities to BCC in vivo on more than 20 different cell markers.. This study provides a simple technique for establishing pure cell cultures of nodular BCC and describes extensively the in vitro parameters of tumor cell growth. The striking differences in behavior of cultured tumor cells in the presence or absence of normal-appearing keratinocytes suggest that normal human epidermal keratinocytes can suppress the growth of BCC cells.

Topics: Adult; Aged; Animals; Antibodies, Neoplasm; Antigens, Neoplasm; Carcinoma, Basal Cell; Cell Division; Female; Filaggrin Proteins; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Rabbits; Skin Neoplasms; Tumor Cells, Cultured

Expression of human leukocyte elastase inhibitor, elafin, otherwise known as skin-derived antileukoproteinase inhibitor (SKALP), was investigated in normal and abnormal oral tissues using a specific anti-SKALP rabbit antiserum. Weak staining was observed in keratinizing epithelia of normal oral mucosa but not in non-keratinizing mucosa. Increased expression was also observed in the suprabasal layers of dysplastic oral epithelia and in well-differentiated squamous cell carcinoma, but not in basal cell carcinoma. A uniform strong expression was observed in all supra-basal layers of odontogenic keratocyst epithelia, except in regions where inflammatory infiltrate was adjacent to keratocyst epithelia. In contrast, elafin expression in a small number of dentigerous cysts and ameloblastomas was more patchy. The increased levels of elafin in keratocyst epithelia and dysplastic tissue may be a cellular homoeostatic response to generate a protective barrier preventing proteolytic degradation of underlying elastic tissue.

Topics: Ameloblastoma; Animals; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dental Sac; Dentigerous Cyst; Elastic Tissue; Epithelium; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Gingiva; Homeostasis; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Odontogenic Cysts; Peptide Hydrolases; Proteinase Inhibitory Proteins, Secretory; Proteins; Rabbits; Serine Proteinase Inhibitors

Tumor of the follicular infundibulum is a rare proliferation of cells and its histogenesis or differentiation at the morphological level has been the subject of some controversy. In recent years cytokeratins have been recognized as important markers of epithelial differentiation, and of late new retrieval methods have meant it is possible to detect them in formalin-fixed and paraffin-embedded tissue. Four patients were studied, the ages ranging between the 2nd and 7th decade. The tumors were all located in the head and neck and in one case the lesion developed in a pre-existing sebaceous nevus. The morphological investigation revealed a flat, proliferation of polygonal, pale eosinophilic cells connected to epidermis or follicular infundibulum and with a centrally located nucleus. In addition, a few ductal structures resembling sebaceous ducts were seen and in one case a hair germ papilla and a follicular papilla was noted. Immunohistochemical investigations with antibodies against cytokeratins revealed differentiation comparable to that in the fetal follicular isthmus and, in one case, also differentiation in keeping with the fetal follicular infundibulum.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Cytoplasm; Female; Hair Follicle; Hamartoma; Head and Neck Neoplasms; Humans; Keratinocytes; Keratins; Male; Middle Aged; Precancerous Conditions; Sebaceous Glands; Skin Neoplasms

Topics: Acrospiroma; Aged; Arsenites; Biomarkers, Tumor; Biopsy; Carcinoma, Basal Cell; Diagnosis, Differential; Humans; Keratins; Keratoderma, Palmoplantar; Male; Neoplasms, Multiple Primary; Potassium Compounds; Precancerous Conditions; Skin; Skin Neoplasms

A 69 yr old man had a 4 mm basal cell carcinoma completely excised from the chin. Numerous hyaline cytoplasmic inclusions were contained within the tumor cells. The inclusions stained intensely red with Masson's trichrome, and immunocytochemically there was prominent rim labelling for keratins (bovine, callus and AE1/3) and muscle-specific actin, the latter more faintly decorating the centre of some inclusions. The inclusions were negative for antibodies to cytokeratin Cam5.2, epithelial membrane antigen (EMA), vimentin, S100, neurofilaments, glial fibrillary acidic protein (GFAP) and carcinoembryonic antigen (CEA) and there was no post Congo red apple green birefringence to indicate amyloid. Ultrastructure indicated the inclusions were composed of proteinaceous material surrounded by a defined rim of tonofilaments in cells showing no degenerative features. The findings suggested aberrant tumor cell keratinization. Familiarization with this rare variant of a common cutaneous carcinoma will alleviate diagnostic difficulties that may arise, particularly in superficial tumor curettage.

Topics: Aged; Carcinoma, Basal Cell; Chin; Humans; Hyalin; Immunohistochemistry; Inclusion Bodies; Keratins; Male; Microscopy, Electron; Skin Neoplasms

Topics: Aged; Carcinoma, Basal Cell; Cysts; Humans; Keratins; Male; Skin Diseases; Skin Neoplasms

In micrographic (Mohs') surgery, routine haematoxylin and eosin stains may present difficulties in interpretation of infiltrative (morphoeic) basal cell carcinoma. To supplement these routine stains rapid immunoperoxidase and immunofluorescence techniques are described using cytokeratin markers Dako LP34, MNF 116 or Novocastra NCL-Pan CK on frozen sections to help in the histological evaluation of these tumours.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Mohs Surgery; Skin Neoplasms

The incidence of Merkel cells has previously been investigated in a number of inflammatory and tumorous lesions of the skin. Special attention was given to tumors with follicular differentiation. In the present study we examined the localization of Merkel cells in another adnexal tumor, the desmoplastic trichoepithelioma (n = 15), as well as in its main differential diagnosis, the morpheiform basal-cell carcinoma (n = 30). Using immunohistochemical methods, we found Merkel cells as a stable constituent in desmoplastic trichoepitheliomas, but failed to detect them in morpheiform basal-cell carcinomas. These findings might therefore be an important tool in the sometimes very difficult but clinically imperative distinction between these two conditions. Furthermore, our study may be of interest in the discussion about the origin of desmoplastic trichoepitheliomas. High numbers of Merkel cells in desmoplastic trichoepitheliomas indicate a bulge-derived origin of this adnexal tumor, since high numbers of Merkel cells, especially in the bulge, were recently discovered. Although the significance of Merkel cell hyperplasia in desmoplastic trichoepithelioma is not presently understood, a regulatory role of the Merkel cell in growth and development of this adnexal tumor is suggested.

Topics: Carcinoma, Basal Cell; Chromogranin A; Chromogranins; Epidermis; Hair Follicle; Humans; Immunohistochemistry; Keratins; Merkel Cells; Microscopy, Electron; Neoplasms, Basal Cell; Skin Neoplasms

Nevus sebaceus, considered to be a hamartoma, is known to develop several secondary hyperplastic and neoplastic proliferations. By the use of immunohistochemical studies, we were able to describe a sometimes very striking increase of Merkel cells in nine of 19 nevi sebacei. Only nevi sebacei that formed follicular germ structures and trichoblastomas showed a Merkel cell hyperplasia. In the hyperplastic epidermis of some cases a slight hyperplasia of singular Merkel cells was observed. In foci with follicular germs and trichoblastomas, however, the Merkel cells were much more abundant and sometimes arranged in clusters. Merkel cell hyperplasia is likely to represent another facet of hamartomatous hyperplasia in nevi sebacei. Our observation that trichoblastomas in nevus sebaceus possess, as a rule, hyperplasia of Merkel cells, might be an additional aid to distinguish these tumors from basal cell carcinomas, which are usually devoid of Merkel cells. Furthermore, our findings are a hint that development of follicular germs and trichoblastomas in nevi sebacei may be promoted by Merkel cells.

Topics: Adolescent; Carcinoma, Basal Cell; Cell Count; Child; Chromogranin A; Chromogranins; Coloring Agents; Diagnosis, Differential; Epidermis; Hair Follicle; Hamartoma; Humans; Hyperplasia; Immunohistochemistry; Keratins; Merkel Cells; Neoplasms, Basal Cell; Skin; Skin Abnormalities; Skin Neoplasms

Metastatic basal cell carcinomas of the skin are rare. We present the cytologic features of a metastatic basal cell carcinoma to the lung diagnosed by fine-needle aspiration biopsy. Cytologic examination revealed syncytial groups of relatively small cells with hyperchromatic, oval to spindle-shaped nuclei having high nuclear to cytoplasmic ratios. Immunocytochemical studies performed on the cell block sections revealed the malignant cells to be positive for cytokeratin (AE1/3) and negative for neuroendocrine markers, [neuron specific enolase (NSE) and chromogranin (Phe-5)]. We reviewed the literature related to metastatic basal cell carcinoma of the skin and discuss risk factors and mechanisms of metastatic spread. In addition, a discussion of the other entities that can enter into the differential diagnosis is presented along with the role of ancillary studies. To the best of our knowledge, we believe this is the first case report of the fine-needle aspiration (FNA) cytology of a basal cell carcinoma metastatic to the lung.

Topics: Biopsy, Needle; Carcinoma, Basal Cell; Female; Humans; Intermediate Filaments; Keratins; Lung Neoplasms; Middle Aged; Skin Neoplasms

We describe 13 cases of tricholemmal carcinoma, a rarely recognized cutaneous adnexal neoplasm. The patients were nine men and four women. In general, the tumors presented as slow-growing epidermal papules, indurated plaques, or nodules showing predilection for sun-exposed, hair-bearing skin. The lesions were most frequently misdiagnosed clinically as basal cell carcinoma. Histologically, they showed a variegation of growth patterns including solid, lobular, and trabecular; they were characterized by a proliferation of epithelial cells with features of outer root sheath differentiation, including abundant glycogen-rich, clear cytoplasm, foci of pilar-type keratinization, and peripheral palisading of cells with subnuclear vacuolization. Because of their variable growth pattern, overt cytologic atypia, abundant clear cytoplasm, occasional pagetoid intraepidermal spread, and brisk mitotic activity, these tumors may pose difficulties for diagnosis and be confused with other malignant skin tumors with clear cell changes. Despite the seemingly malignant cytological appearance of these lesions, clinical follow-up in 10 cases showed no recurrence or metastasis over a period of 2-8 years. Thus, conservative surgical excision with clear margins appears to be the treatment of choice for these neoplasms.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoplasm; Diagnosis, Differential; Epidermal Cyst; Epithelium; Female; Follow-Up Studies; Glycogen; Hair Diseases; Humans; Keratins; Male; Middle Aged; Mitosis; Neoplasms, Basal Cell; Skin Diseases; Skin Neoplasms; Vacuoles

Topics: Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Neoplasm Metastasis; Skin Neoplasms

The presence and distribution of several cytokeratins (CKs) in 20 solid basal cell epitheliomas (BCEs) were investigated and compared with the pattern of CKs in normal epidermis, perilesional skin and in the outer root sheath (ORS) of the human hair follicle. Tissue samples were stained with monoclonal antibodies (MoAbs) against human CKs, using the APAAP technique. Additionally, CK profiles were assessed by gel electrophoresis and immunoblot technique. Cells of BCE and ORS were positively stained with the MoAb KL1, whereas the basal layer of normal epidermis remained negative. Six out of 20 BCEs were partially stained with the MoAb RPN1165, which also stained the lower ORS, but not the epidermal basal layer. Using SDS-PAGE and immunoblot, the CK profiles of BCE and ORS were almost identical, showing the presence of CKs 5, 6, 14, 16 and 17; the CK pattern of normal epidermis, however, showed the presence of CKs 1, 5, 10 and 14. Perilesional skin (< 5 mm) showed keratin changes similar to the BCE pattern; the basal layer was stained with the MoAb KL1 and the suprabasal layer was negative to MoAb CK1, in contrast to normal epidermis. Keratin analysis revealed a CK pattern of perilesional skin different from that of normal epidermis (CKs 1, 5, 6, 10, 14, 16 and 17). Our immunohistochemical and biochemical investigations underline the possible role of the lower ORS as a cellular pool for the generation of BCE.

Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Hair; Humans; Keratins; Scalp; Skin Neoplasms; Staining and Labeling

We have identified strong expression of a 38-kD cell surface glycoprotein (gp38), a marker of basal cell carcinomas (BCCs), in basal and suprabasal epithelial cell membranes of parakeratinised odontogenic keratocysts. In contrast, orthokeratinised cysts and most other odontogenic cyst types, ameloblastomas, normal stratified oral epithelium, cell rests of Malassez and glands of Serres, all proved negative. To our knowledge this is the first histochemical marker to distinguish between these major cyst types. It has obvious uses in the diagnosis of inflamed keratocysts and the separation of ameloblastomas from BCCs and may find a role in studies of the developmental biology of other odontogenic structures.

Topics: Antibodies, Monoclonal; Biomarkers; Biomarkers, Tumor; Carcinoma, Basal Cell; Dental Enamel; Epithelium; Gene Expression Regulation; Glycoproteins; Humans; Keratins; Membrane Glycoproteins; Mouth Mucosa; Nonodontogenic Cysts; Odontogenic Cysts; Periapical Granuloma; Periodontitis

Sebaceous carcinoma is an infrequent skin tumor and its histological features sometimes closely resemble those of squamous cell carcinoma (SCC) and basal cell epithelioma (BCE), which often leads to a misdiagnosis. In the present immunohistochemical study, however, sebaceous carcinoma exhibited quite a different expression of keratins from SCC and BCE. We immunohistochemically examined 26 excised specimens of sebaceous carcinoma, 10 of SCC and 12 of BCE of the eyelids, using two monoclonal antibodies against high molecular weight keratins, 34 beta B4 (68kd) and 34 beta E12 (56kd, 56.5kd, 58kd), and two monoclonal antibodies against low molecular weight keratins, 35 beta H11 (54kd) and CAM5.2 (39kd, 43kd, 50kd). The cases of sebaceous carcinoma were positive with 34 beta B4 (23%), 34 beta E12 (54%), 35 beta H11 (81%) and CAM5.2 (73%). Of the four anti-keratin antibodies used in this study, 35 beta H11 was negative in all cases of SCC or BCE. These findings indicate that when sebaceous carcinoma is suspected, but no fat staining appropriate materials are available, a monoclonal antibody against low molecular weight keratin, 35 beta H11 (54kd), can be a useful tool to immunohistochemically rule out both SCC and BCE.

Topics: Adenocarcinoma, Sebaceous; Adenoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Molecular Weight; Sebaceous Gland Neoplasms; Skin Neoplasms

Recent studies of an endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan are focusing on its cytokeratin analysis in hopes of tracing the disease's biochemical expression. Specimens were obtained from uninvolved skin and arsenical cancers including Bowen's disease, basal cell carcinoma, and squamous cell carcinoma. In this study, we used two-dimensional polyacrylamide gel electrophoresis to analyse cytokeratin expression. Progressive alterations in cytokeratin expression were found in various skin lesions. These include an expression of K16 in the uninvolved skin; K16 and K6 in Bowen's disease; and K16, K6 and K17 in squamous cell carcinoma and basal cell carcinoma. In addition, we found that the K1 isoelectric variants shifted to more acidic forms with the complete absence of K1 in basal cell carcinoma. K16 expression in uninvolved skin indicates that it is nevertheless in a hyperproliferative status. K17 was expressed in squamous cell carcinoma and basal cell carcinoma, but not in Bowen's disease. The progressive impairment of phosphorylation of K1 and K2 in the process of chronic arsenism provides us with a suitable model for studying the biological significance of phosphorylation in intermediate filaments during chemical carcinogenesis.

Topics: Arsenic Poisoning; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chronic Disease; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Poisoning; Skin; Skin Neoplasms; Taiwan

Whether the peripheral ameloblastoma (PA) and intraoral basal cell carcinoma (BCC) are two different clinical entities or essentially the same lesion still remains unresolved. The immunophenotypes of neoplastic cells of peripheral and intraosseous ameloblastomas, ameloblastic carcinomas, and BCCs were studied using a panel of monoclonal/polyclonal antibodies and lectins. The major cytokeratins (CKs) of neoplastic cells of ameloblastomas were CKs 5 and 14, whereas co-expression of CKs 8, 18, and 19 was observed in the cells of the stellate reticulum-like areas. Metaplastic squamous and keratinizing cells found in follicular and acanthomatous variants of ameloblastomas expressed CKs 1 and 10, involucrin, and binding sites for the lectins Ulex europeaus agglutinin I and Helix pomatia agglutinin. beta 2-Microglobulin was uniformly negative in all cases of ameloblastomas and ameloblastic carcinomas studied. Cutaneous BCCs also demonstrated similar reactive patterns with the above-mentioned antigens. The most striking feature is the presence of a peritumorous band-like peanut agglutinin staining found in both BCCs and PAs but not in intraosseous ameloblastomas. This unique peanut agglutinin staining pattern of PA may be diagnostically useful for its histopathologic distinction from an intraosseous ameloblastoma that has infiltrated the soft tissue. The neoplastic cells of ameloblastomas express markers of less-differentiated epithelial cells. Despite differences in epithelial origins, PAs are tumors analogous to cutaneous BCCs.

Topics: Adolescent; Adult; Aged; Ameloblastoma; Antigens, Differentiation; beta 2-Microglobulin; Bone Neoplasms; Carcinoma, Basal Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lectins; Male; Middle Aged; Protein Precursors; Receptors, Mitogen; Skin Neoplasms; Soft Tissue Neoplasms

Granular cell basal cell carcinoma (BCC) is a rare histological variant of BCC. In this, the fifth reported case, a 67-year-old male with BCC located on the nose, light microscopy examination showed a tumour with the classical configuration of nodular BCC, in which most cells had finely granular eosinophilic cytoplasm. Ultrastructural observation showed numerous lysosome-like granules filling the cytoplasm of tumour cells, along with numerous well-formed pentalaminate desmosomes. Immunohistochemical profile (including positivity for keratins C 5.2 and AE 1 and for Leu-M1), together with the presence of cytoplasmic tonofilament bundles and desmosomes, are consistent with the proposed epithelial origin of granular cells in this tumour.

Topics: Aged; Carcinoma, Basal Cell; Cytoplasm; Desmosomes; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Skin Neoplasms

We have examined the character and carcinogenic properties of the normal-appearing epidermis overlying basal cell carcinomas by immunohistochemical methods, employing a series of monoclonal antibodies. The labelling index was significantly increased in the atrophic epidermis overlying basal cell carcinomas (solid type, n = 20), compared with the epidermis overlying or adjacent to squamous cell carcinoma (n = 20), keratoacanthoma (n = 10), dermatofibroma (n = 10), neurofibroma (n = 10), soft fibroma (n = 10), pyogenic granuloma (n = 10) and cutaneous leiomyoma (n = 5). Cells which expressed epidermal growth factor (EGF) receptor were detected in all layers of the epidermis over the basal cell carcinomas, but not the other tumours. Basement membrane-related antigens, including bullous pemphigoid antigen and GB3 antigen, were decreased in the epidermis. AE1, the monoclonal antibody against basal cell keratin, reacted with the uppermost layers of the normal-appearing epidermis overlying the basal cell carcinomas. ICAM-1 expression was very weak in the overlying epidermis. The dermis subjacent to the proliferating epidermis showed staining for transforming growth factor-alpha (TGF-alpha), strong positive PECAM-1 staining of endothelium, and numerous HLA-DR-positive cells. From these results, we suggest that the proliferative activity in the epidermis overlying basal cell carcinomas is not a state induced by the dermal infiltrate, but represents carcinogenic activity of the epidermis.

Topics: Antibodies, Monoclonal; Antigens, CD; Autoantigens; Basement Membrane; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Adhesion Molecules; DNA; Epidermis; ErbB Receptors; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Keratins; Skin Neoplasms; Transforming Growth Factor alpha

Two additional cases of cutaneous lymphadenoma (CL) are reported. The lesions presented as single nodules of many years' duration on the face. Histologically, the neoplasms consisted of irregularly shaped lobules immersed in a dense fibroblastic stroma involving the whole dermis and extending into the subcutaneous fat. Duct-like structures suggesting an eccrine differentiation were recognized. The lobules were composed of a rim of basaloid cells surrounding large epithelioid cells and lymphocytes. In some areas the basaloid lobules were only partly replaced by the inflammatory cells. Immunohistochemically, the intralobular inflammatory component was composed of a mixed B- and T-cell population and S-100-positive dendritic cells. The observation of these cases suggests that CL is not a distinct entity but may represent a basal cell carcinoma, possibly with pilar or eccrine differentiation, in which an immune host reaction pattern is exceedingly unusual.

Topics: B-Lymphocytes; Carcinoma, Basal Cell; Cheek; Diagnosis, Differential; Epithelium; Facial Neoplasms; Female; Fibroblasts; Humans; Keratins; Lymphoma; Male; Middle Aged; S100 Proteins; Skin Neoplasms; T-Lymphocytes

The tissue labelling of a panel of monoclonal antikeratin antibodies (LL001, LL002, LL003, LP2K, BA17, LP34, CAM5.2, and LH1) recognising keratins 1, 5, 8, 10, 14, 18, and 19 were investigated in frozen and formalin-fixed normal skin. Antibodies LL001, LL003, BA17, LP34, CAM5.2, and LH1 were found to be reactive in formalin-fixed material and were used to study 23 basal cell carcinomas, 8 squamous cell carcinomas, 5 keratoacanthomas, 5 Bowen's disease, and 6 clear cell acanthomas. All these tumours demonstrated a loss of keratin 10 expression as demonstrated by loss of labelling with LH1. Keratin 14 expression, as demonstrated by LL001, was reduced but present in all the tumours except squamous cell carcinomas and keratoacanthomas where increased labelling was observed in the more differentiated areas of these tumours. Simple epithelial keratin expression was demonstrated by positive labelling with CAM5.2 and keratin 19 by BA17 in a third of basal cell carcinomas and squamous cell carcinomas. Three of the five keratoacanthomas labelled with BA17, indicating the presence of keratin 19 in these lesions. These results support the concept that keratin expression is a phenotypic marker of the state of differentiation or malignant transformation and that patterns of keratin expression are not specific to any particular premalignant or malignant disorder.

Topics: Antibodies, Monoclonal; Axilla; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Freezing; Humans; Immunohistochemistry; Keratins; Keratoacanthoma; Reference Values; Skin; Skin Neoplasms; Tissue Fixation

The keratin phenotype of 15 cases of basal cell carcinoma was assayed immunohistochemically using a panel of monospecific antibodies to single keratin polypeptides. Whilst tumour tissue strongly expressed primary keratins 5 and 14 (normally synthesized in basal keratinocytes) no expression of secondary keratins 1 and 10 (characteristic of skin-type differentiation) was detected. Keratin 17, characteristic of the outer hair root sheath, was strongly expressed in all tumours. Keratin 19 was also normally expressed in parts of the hair follicle and was detected in four cases. The 'high cell turnover' keratin 16 was frequently induced in the overlying epidermis, but was rare within tumour tissue. No expression of simple epithelial keratins 8 and 18 was detected. Whilst the keratin phenotype of tumour cells is similar to that of basal cells within part of the hair root sheath, in keeping with suggestions of a follicular origin for basal cell carcinomas, the findings are also compatible with an origin from interfollicular pluripotent stem cells differentiating towards follicular structures.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Basal Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mice; Rabbits; Skin Neoplasms

Lectins bind tightly to carbohydrate moieties on cell surfaces. Alterations in lectin binding have been reported to accompany epidermal cell differentiation, marking alterations in membrane sugars during this process. The presence of UEA I (Ulex europaeus agglutinin I) L-fucose-specific lectin-binding sites has been used as a marker for terminally differentiated (committed) keratinocytes. In this article, we report the presence of UEA-I-binding sites on squamous keratinocytes of well-differentiated squamous cell carcinomas, with patchy loss of UEA I positivity on poorly differentiated cells of squamous cell carcinomas, suggesting a possible use for this technique in the rapid assessment of less differentiated areas within the squamous cell tumor. The absence of UEA-I-binding sites on basal cell carcinomas may be related to an inability of cells comprising this tumor to convert the L-D-pyranosyl moiety on basal cells to the L-fucose moiety, resulting in an inability of basal cell carcinoma cell to undergo terminal differentiation into a committed keratinocyte.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Endothelium, Vascular; Epidermis; Epithelium; Fucose; Humans; Keratinocytes; Keratins; Lectins; Plant Lectins; Receptors, Cell Surface; Receptors, Mitogen; Skin Neoplasms

On review of 115 poorly or undifferentiated lung cancers from 671 lung tumors resected over a 7-year period, we have found 38 cases of basaloid carcinoma. The cardinal histopathologic features distinguishing this tumor from other non-small cell lung cancers are a lobular growth pattern of small cells with moderately hyperchromatic nuclei, with no prominent nucleoli, and with scant cytoplasm, a high mitotic rate, and peripheral palisading. Basaloid carcinoma was present in a pure form in 19 cases and the other 19 tumors were of a mixed, but prominent, basaloid type associated with squamous cell carcinoma, large cell carcinoma, or adenocarcinoma. The immunophenotype of basaloid cancers was close to that of basal bronchial epithelial cells, with a low level of expression of low molecular weight cytokeratins. Staining for neuroendocrine markers was infrequent and inconsistent. Ultrastructural study showed an absence of neurosecretory granules and the presence of some squamous and/or glandular differentiation. This morphologic and immunologic phenotype suggests that basaloid carcinoma is derived from a pluripotent reserve cell or a basal bronchial epithelial stem cell. This unique histologic form of lung tumor has a poor prognosis, with a median survival rate of 22 months for stage I and II disease. This justifies classification of basaloid carcinoma as a distinct form of lung cancer, separate from small cell lung carcinoma.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Microscopy, Electron; Middle Aged; Neoplasm Staging; Phenotype; Prognosis; Survival Analysis

Cell cultures were established from 48 solid basal cell carcinomas (BCC) and from the normal epidermis of the same patients. The growth characteristics and differentiation of BCC cells in vitro were compared with normal keratinocytes (nKC) by using immunohistochemistry, two-dimensional gel electrophoresis including immunoblots, transmission electron microscopy, and soft agar suspension culture. After isolation of the tumor tissue under a stereodissection microscope, explants were cultured on feeder layers of mitomycin-treated 3T3 cells. After 3-5 d, 73% of all explants of BCC could be successfully cultured showing spindle-shaped outgrowing cells. Compared to nKC, cultured BCC cells had a lower growth rate and showed a wider intercellular polymorphism regarding size and shape. Their labeling pattern with a wide panel of monoclonal antibodies showed significant differences from that of nKC. In particular, only weak reactions for various cytokeratins, filaggrin and vimentin depending on the BCC cell type (small, middle, large) were found. Two-dimensional gel electrophoresis revealed expression of keratins 5, 6, 14, 16, and 17 in BCC cells and of K 5, 6, 13, 14, 16, 17, and 19 in nKC. These findings were confirmed by immunoblot. On the ultrastructural level, only a few desmosomes and a lower degree of keratinization markers were detected in BCC cells; finally, when cultured in soft agar BCC cells formed colonies whereas nKC did not. Our findings indicate that cultured BCC cells may preserve in vitro some in vivo characteristics and maintain a growth and differentiation pattern that differs from cultured nKC. The culture model presented here provides further insights into the cytogenetic and histogenetic characteristics of BCC.

Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Cells, Cultured; Electrophoresis, Gel, Two-Dimensional; Female; Filaggrin Proteins; Humans; Immunohistochemistry; Keratinocytes; Keratins; Male; Microscopy, Electron; Middle Aged

In the epithelium of secretory acini of the prostate two different cell types can be discriminated on the basis of localization, morphology, and degree of differentiation, the luminal and basal cells. The possibility of a developmental relationship between basal and luminal cells has been a subject of interest in several studies. According to the stem cell model at least three cell types, i.e., stem, amplifying, and transit cells, can be discriminated in the epithelium of prostate secretory acini. We previously reported that in the process of degeneration and regeneration in normal rat prostate a population of cells could be identified as candidates for the amplifying cells. These cells showed a keratin expression profile intermediate between those of basal and luminal cells. We now show, by using keratin antibodies, that also in normal human prostate at least three subpopulations of cells can be identified, one of them putatively representing amplifying cells as defined in the stem cell model. Furthermore, these antibodies were used to obtain a better insight into the different cell types involved in the etiology and progression of prostatic carcinoma. Both primary and hormone-independent prostatic tumors were investigated. Our results indicated that the candidate stem cell population was absent in prostatic carcinoma. Unlike earlier reports on the unique presence of cells with luminal characteristics in prostatic carcinoma, we identified also a population of cells coexpressing basal and luminal cell-type cytokeratins in primary and hormone-independent prostatic carcinoma. Since amplifying cells are defined in the stem cell model as precursors of transit (luminal) cells in the hierarchical pathway of prostatic epithelium differentiation, we postulate that on the basis of the keratin expression profile this subpopulation is most likely the target for neoplastic transformation.

Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Cell Differentiation; Humans; Immunoblotting; Immunophenotyping; Keratins; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms

Formalin-fixed, paraffin-embedded biopsy specimens of 17 cases of squamous cell carcinoma of Marjolin's ulcer (SCC-MU), 6 cases of common SCC (SCC), and 5 cases of basal cell carcinoma (BCC) were stained with three monoclonal antikeratin antibodies (CAM 5.2, MAK-6, and MA-903), a monoclonal antivimentin antibody (V9), and a polyclonal anticarcinoembryonic antigen antiserum (A115). Neoplastic cells of SCC-MU, SCC, and BCC showed consistently negative staining for CAM 5.2. A wide range of reactivity, from negative to diffuse strong positivity, among neoplastic cells of SCC-MU and SCC was noted with MAK-6. Alternatively, neoplastic cells of SCC-MU, SCC, and BCC consistently showed diffuse moderate to strong reactivity with MA-903. These findings imply that SCC-MU has largely high-molecular-weight keratins. They also showed a wide range of reactivity with V9. However, neoplastic cells of five of the six SCC and five cases of BCC were negative for V9. These findings suggest that neoplastic cells of SCC-MU contain vimentin in higher frequency than in the more usual SCC.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biopsy; Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cicatrix; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin; Skin Neoplasms; Ulcer; Vimentin

Gene K51 probe isolated previously from the rat genomic library has been used to study the expression of its human counterpart by in situ hybridization and Northern blot analysis. A polyA-containing transcript of human gene K51 of 3 kb size has been detected in embryonic skin. The gene is also expressed in the epidermis of newborn humans and adults, but not in the adjacent mesenchymal tissues. Immunostaining with keratin antisera revealed predominantly earlier stage expression of K51 than cytokeratin markers. Sebaceous and sweat glands also contain cells expressing K51 gene. K51 expression was found in the cells of eight individual basal cell carcinomas tested, with the level of expression lower than in keratinocytes from normal human epidermis. We propose that K51 gene expression could serve as a convenient marker for the study of the process of skin keratinocyte development and the changes in this process associated with skin cancers and dysplasia.

Topics: Blotting, Northern; Carcinoma, Basal Cell; Epidermal Cells; Epidermis; Gene Expression Regulation, Neoplastic; Genes; Humans; Immunohistochemistry; Keratinocytes; Keratins; Skin Neoplasms

Comparative immunomorphological study of keratinous proteins was performed in 17 basaliomas, 4 metatypical (MT) and 1 squamous cell carcinomas by means of a spectrum of antibodies to the individual keratins. It is found that cells of MT carcinoma are distinguished from basalioma cells by the absence of keratins N8 and 17 and this may be used for the differential diagnosis of these two tumours. The spectrum of keratins expressed by basalioma cells coincides with that of early stages of hair follicles. Keratin N17 is locally induced in parabasal layers of the morphologically intact epidermis adjacent to the tumour.

Topics: Aged; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Keratins; Middle Aged; Neoplasm Proteins; Skin Neoplasms

25 skin basaliomas were studied immunohistochemically using 6 different monoclonal antibodies (MAB) to the low-molecular cytokeratins N 8, 18 (according to Moll's catalog) as well as to the cytokeratins N 1, 2, 9, 10, 11 and N 17. Prekeratin N 17 was found in all tumours while cytokeratin N 18 was found in no tumour. Prekeratin N 8 was expressed in 24% of tumours. MAB EE 21-06 to the cytokeratin N 1, 2, 9, 10, 11 are reactive with tumour cells in 20% of cases. Basalioma cells (apart from trichobasalioma) did not react with MAB G 36-19. These results suggest a dissimilar origin of basaliomas and may help in the differential diagnosis of the skin malignant tumours.

Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Molecular Weight; Skin Neoplasms

Using immunohistochemical methods, we investigated the distribution of epithelial membrane antigen (EMA) on the normal eccrine gland, eccrine poroma and hidroacanthoma simplex. Granular membrane-associated reaction of EMA was detected on the outer cells of both the intraepidermal and the upper portion of intradermal eccrine ducts, as well as on the luminal surfaces and intercellular canaliculi of eccrine glands. Clear immunolabeling was also present in the tumor cells of eccrine poroma and hidroacanthoma simplex. Thus, it is suggested that the constituent cells of these tumors originate from the outer cells of the intraepidermal and/or the upper portion of the intradermal eccrine ducts. There was no immunolabeling for EMA on the tumor cells of seborrheic keratosis and basal cell carcinoma. Immunohistochemical staining for EMA is a useful tool for the diagnosis of skin appendage tumors.

Topics: Adenoma, Sweat Gland; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Basal Cell; Cell Membrane; Cytoplasm; Dermatitis, Seborrheic; Eccrine Glands; Epithelium; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Reproducibility of Results; Skin Neoplasms

Cutaneous horns usually represent compacted keratin arising from an underlying pathologic process and are important to dermatologists because they may indicate an underlying malignancy. The differential diagnosis of cutaneous horns includes pseudohorns, which have the morphologic appearance of a cutaneous horn but consist entirely of benign or malignant tumor. We describe a second type of pseudohorn consisting of hair, dried serum, and inflammatory exudate that was associated with an underlying basal cell carcinoma.

Topics: Carcinoma, Basal Cell; Diagnosis, Differential; Female; Humans; Keratins; Middle Aged; Skin; Skin Neoplasms; Staphylococcal Skin Infections

We describe a case of clear cell basal cell carcinoma of the superficial type, presenting as a crusted eruption on the abdomen. Histological examination showed a solid proliferation of clear cells attached to the under-surface of an atrophied epidermis. In addition, distinct pagetoid infiltration was seen within the overlying epidermis. A focal connection between the clear cell portion and a deeper lying nodular basal cell carcinoma was demonstrated, elucidating the true nature of the lesion. Immunohistochemical studies and electronmicroscopy confirmed the epithelial derivation of the tumour. The clear cell appearance was due to multiple cytoplasmic electronlucent vacuoles which were not surrounded by membranes.

Topics: Abdomen; Carcinoma, Basal Cell; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Middle Aged; Organelles; S100 Proteins; Skin Neoplasms; Vimentin

The neu (c-erbB-2) gene encodes a transmembrane protein with tyrosine kinase activity that appears to be a growth factor receptor. Antibody was generated by immunization of rabbits with a synthetic polypeptide that was based on an internal sequence at the carboxy terminus of the molecule. This antibody was used to survey the expression of neu in human skin by immunohistochemistry. Significant protein was found in the squamous cell layer of the surface epidermis, in squamous cell carcinomas, in the external root sheath of hair follicles, and in eccrine gland secretory cells; it was poorly expressed in the basal cell layer and in a basal cell carcinomas. Increased neu expression appears to be associated with the differentiation of keratinocytes.

Topics: Antibody Specificity; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Line, Transformed; Epidermal Cells; Humans; Immunoenzyme Techniques; Keratins; Precipitin Tests; Proto-Oncogene Proteins; Receptor, ErbB-2; Skin; Skin Neoplasms

We used an avidin-biotin complex immunoperoxidase technique with various monoclonal antibodies to determine Langerhans cell densities, class II antigen expression on keratinocytes, and phenotypes of other infiltrating cells in several malignant and benign epithelial tumors of the skin. Our observations indicate (1) there are few Langerhans cells in nests of basal cell carcinoma and squamous cell carcinoma; (2) there are increased Langerhans cell densities in seborrheic keratoses, verrucous epidermal nevus, and Bowen's disease; (3) there is an expression of class II molecules on the keratinocytes and cancer cells of basal cell carcinoma, squamous cell carcinoma, Bowen's disease, seborrheic keratosis, and verrucous epidermal nevus; and (4) there is a netlike staining of the keratinocyte surface with OKM5 in the epidermal lesion of seborrheic keratosis, verrucous epidermal nevus, and Bowen's disease, as well as in the epidermis adjacent to the basal cell carcinoma and squamous cell carcinoma nests.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Bowen's Disease; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermal Cells; Female; Histocompatibility Antigens Class II; Humans; Keratins; Keratosis; Langerhans Cells; Male; Middle Aged; Skin Neoplasms

Measurement of colony-forming ability following exposure to gamma-rays was performed on cultured skin keratinocytes and skin fibroblasts obtained from normal individuals, basal cell naevus syndrome patients (BCNS) and ataxia telangiectasia (A-T) patients. The most striking observation was the radiation resistance of 8/8 keratinocyte strains compared with fibroblasts whether from BCNS patients or normals. The single A-T keratinocyte cell strain showed the same radiosensitivity as A-T fibroblast cell strains. The differential survival of keratinocytes and fibroblasts was also observed following exposure to 254 nm UV light. The survival curves of SV40 immortalized keratinocytes and retinoblasts derived from normal individuals or BCNS patients showed large shoulder regions following exposure to gamma-rays or 254 nm UV light. An increased D37 rather than an increased D0 was therefore the feature of such curves. This contrasted with the SV40 immortalized A-T keratinocytes or fibroblasts which showed a minimal shoulder effect and an increased D0. No difference in survival was observed between BCNS and normal cells following exposure to either UV or gamma-rays.

Topics: Ataxia Telangiectasia; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Cell Survival; Cobalt Radioisotopes; Epidermal Cells; Epidermis; Fibroblasts; Gamma Rays; Humans; Keratins; Skin; Ultraviolet Rays

Carcinoembryonic antigen (CEA) has been studied extensively, in association with visceral tumors and normal tissues. Although CEA has been demonstrated in sweat gland cutaneous tumors, little is known about its presence in skin and epithelial related tumors. We studied the presence of CEA and keratin in squamous cell and basal cell carcinoma using immunohistochemical techniques. Its distribution related with differentiation, proliferation and malignant potential is observed. The expression of both antigens is correlated.

Topics: Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Skin Neoplasms

The distribution of several markers of keratinocyte differentiation was studied in normal epidermis, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs) using the immunoperoxidase technique on frozen sections of punch biopsy specimens. As markers a panel of chain-specific monoclonal antibodies (MoAbs) directed against cytokeratin (CK) 4, 8, 10, 13, 18 and 19, a polyclonal antiserum against involucrin, as well as a MoAb against the epidermal growth factor (EGF) receptor were used. In 15 out of 19 BCCs tested, expression of CK 8 was seen. Only a few individual cells in a limited number of BCCs showed positive staining for CK 4, 18, or 19. No expression of CK 10 was seen except for some foci of cell keratinization. Involucrin was not found in BCCs except for some squamous horn cysts. In all BCC cells expression of EGF receptor was found. In the suprabasal layers of normal epidermis from SCC patients, positive staining for CK 10 was seen. A few individual cells in a limited number of SCCs showed positive staining for CK 4, 8, or 18. Involucrin was expressed in the center of SCCs and in the upper layers of normal epidermis. Expression of EGF receptor was found in all SCC cells. These results demonstrate differences in cellular origin and differentiation between BCC and SCC.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermal Cells; Epidermis; ErbB Receptors; Humans; Immunoenzyme Techniques; Keratins; Protein Precursors; Skin Neoplasms

A 67-year-old woman had a basal cell carcinoma of the forehead containing numerous hyaline cytoplasmic inclusions. Electron microscopic studies revealed that these inclusions were aggregates of cytoplasmic filaments. Immunohistochemical studies demonstrated reactivity for keratin, vimentin, and smooth-muscle myosin in these structures. Because of potential diagnostic difficulties, the pathologist should be aware of this unusual form of basal cell carcinoma.

Topics: Aged; Carcinoma, Basal Cell; Female; Humans; Hyalin; Inclusion Bodies; Intermediate Filaments; Keratins; Neoplasm Recurrence, Local; Skin Neoplasms; Staining and Labeling

In cultured human keratinocytes (NHEK) maintained in medium containing low levels of Ca2+ (0.04 mM) desmoplakin is a component of certain electron-dense bodies in the cytoplasm. These bodies are associated with bundles of intermediate filaments. Upon elevation of the level of Ca2+ in the culture medium to 1.2 mM, desmoplakin first appears at sites of cell-cell contact in association with bundles of intermediate filaments. Subsequently, desmoplakin becomes incorporated into desmosomes in a manner comparable to that seen in mouse keratinocytes (Jones and Goldman: Journal of Cell Biology 101:506-517, 1985). NHEK cells maintained for 24 hr at Ca2+ concentrations between 0.04 mM and 0.18 mM were processed for immunofluorescence, immunoelectron, and conventional electron microscopical analysis. In NHEK cells grown at Ca2+ concentrations of 0.11 mM, desmoplakin appears to be localized in electron-dense bodies associated with intermediate filaments at sites of cell-cell contact in the absence of formed desmosomes. At a Ca2+ concentration of 0.13 mM desmoplakin is arrayed like beads on a "string" of intermediate filaments at areas of cell-cell association. At 0.15 mM, desmosome formation occurs, and desmoplakin is associated with the desmosomal plaque. In basal cell carcinoma cells desmoplakin is not restricted to desmosomes but also occurs in certain electron-dense bodies morphologically similar to those seen in NHEK maintained in low levels of Ca2+ and during early stages of desmosome assembly. We discuss the possibility of "cycling" of desmoplakin through these bodies in proliferative cells.

Topics: Blotting, Western; Calcium; Carcinoma, Basal Cell; Cells, Cultured; Cytoskeletal Proteins; Desmoplakins; Desmosomes; Epidermis; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Microscopy, Electron; Tumor Cells, Cultured

We have undertaken an analysis of hemidesmosomes (HD) and their associated structures, intermediate filaments (IF) and anchoring fibrils (AF), in various types of basal cell carcinoma (BCC). Using a combination of electron microscopy and immunofluorescence microscopy we show that there is a correlation between the loss of HD and tumor type (i.e., in solid and infiltrative BCC hemidesmosomes are present, sometimes in reduced numbers), while there appears to be a lack of hemidesmosomes in cells of sclerosing specimens. Moreover, even though there is a loss of cytoplasmic constituents of the HD in sclerosing forms of BCC, this is not the case with regard to collagen VII, a component of AF, which are normally associated with the extracellular side of the HD. Collagen VII is localized to the basement membrane zone of tumor cells in the absence of the cytoplasmic constituents of HD. Furthermore, deposits of collagen VII occur in the connective tissue close to tumor cell populations in all but one of the BCC specimens we analyzed. In addition to modifications in HD and AF in BCC tissue, there are changes in the cytoskeletal elements of both tumor cells and the normal appearing epidermis that overlies tumor areas. In sclerosing BCC microfilaments are commonly observed along the basal portions of tumor cells where they abut the connective tissue. IF are often found interacting with these microfilaments. Indirect immunofluorescence analysis of tumor tissue using a monoclonal keratin antibody preparation, AE1, which in normal epidermis stains basal cells, reveals that AE1 antibodies only weakly stain tumor cells. Moreover, in the epidermis that overlies tumor cell regions AE1 antibodies stain suprabasal cells and not basal cells. This change in staining pattern generated by AE1 antibodies appears to depend upon the proximity of tumor cells. These results are discussed in relation to the organization of the HD and its associated AF and IF. The possibility that HD, IF, and AF antibody preparations may be of diagnostic use is raised.

Topics: Carcinoma, Basal Cell; Collagen; Cytoskeleton; Desmosomes; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Microscopy, Electron; Skin

We investigated immunohistochemically 20 basal cell carcinomas (BCC), five pilomatricomas, and nine seborrheic keratoses using anti-BCC keratin monoclonal antibody (BKN-1) and anti-hair keratin monoclonal antibodies (HKN-2, HKN-4- -7). The neoplastic cells in all the cases of BCC were always uniformly stained by BKN-1, HKN-2, and HKN-4, indicating that the BCC cells display a constant antigenicity of keratin, which may be different from that of the normal epidermis. Although no fluorescence by HKN-6 or HKN-7 was seen in any cases of BCC, HKN-5 partially but strongly stained the neoplastic nests in most cases of BCC; BCC may have differentiation toward the lower part of hair follicular epithelium. In pilomatricoma, all the anti-keratin monoclonal antibodies showed a similar staining pattern; the differentiating neoplastic cells undergoing transition from basaloid to eosinophilic were positively stained by each antibody in all the cases. This finding of pilomatricoma corresponds to that of the differentiating cells in the inner hair layers, especially in the hair cortex. In seborrheic keratoses, no fluorescence was recognized with HKN-5- -7, which stain the lower follicular cells in the normal human skin. The staining patterns of seborrheic keratosis by BKN-1, HKN-2, and HKN-4 were similar to those of the normal interfollicular epidermis. These anti-keratin monoclonal antibodies seem to be useful for the investigation of the direction of differentiation of skin adnexal neoplasms.

Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Dermatitis, Seborrheic; Humans; Immunohistochemistry; Keratins; Keratosis; Skin Neoplasms

We report here the isolation and characterization of three antisera, each of which is specific for a single keratin from one of the three different pairs (K1/K10, K14/K5, K16/K6) that are differentially expressed in normal human epidermis and in epidermal diseases of hyperproliferation. We have used these antisera in conjunction with monospecific cRNA probes for epidermal keratin mRNAs to investigate pathways of differentiation in human epidermis and epidermal diseases in vivo and in epidermal cells cultured from normal skin and from squamous cell carcinomas in vitro. Specifically, our results suggest that: (a) the basal-specific keratin mRNAs are down-regulated upon commitment to terminal differentiation, but their encoded proteins are stable, and can be detected throughout the spinous layers; (b) the hyperproliferation-associated keratin mRNAs are expressed at a low level throughout normal epidermis when their encoded proteins are not expressed, but are synthesized at high levels in the suprabasal layers of hyperproliferating epidermis, coincident with the induced expression of the hyperproliferation-associated keratins in these cells; and (c) concomitantly with the induction of the hyperproliferation-associated keratins in the suprabasal layers of the epidermis is the down-regulation of the expression of the terminal differentiation-specific keratins. These data have important implications for our understanding of normal epidermal differentiation and the deviations from this process in the course of epidermal diseases of hyperproliferation.

Topics: Amino Acid Sequence; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Transformation, Neoplastic; Cells, Cultured; Epidermal Cells; Epidermis; Humans; Immune Sera; Immunoassay; Immunohistochemistry; Keratins; Molecular Sequence Data; Nucleic Acid Hybridization; Psoriasis; RNA, Messenger; Skin Neoplasms; Tumor Cells, Cultured

Previous observations have demonstrated that fibronectin is deposited in high abundance in basal cell carcinoma stroma. In this study, the nature of fibronectin and the site of its synthesis were explored in 10 basal cell carcinomas of the nodulo-ulcerative type by immunocytochemistry and in situ hybridization. First, simultaneous localization of epithelial tumor cell islands and fibronectin epitopes was carried out by double immunofluorescence staining with monoclonal anti-cytokeratin antibodies and polyclonal fibronectin antibodies, the latter recognizing both the cellular and plasma types of the protein. Large amounts of fibronectin were deposited in the basal cell carcinoma stroma, with the highest concentration present in the immediate proximity of the epithelial cell islands. Immunofluorescence with a monoclonal anti-fibronectin antibody, which is directed against the ED-domain of cellular fibronectin and does not recognize the plasma type of fibronectin, revealed essentially the same staining pattern as that obtained with the polyclonal anti-fibronectin antibody. This observation suggested that fibronectin in BCC was predominantly of the cellular type. Second, in situ hybridizations, utilizing a human fibronectin specific cDNA, demonstrated that the highest concentration of fibronectin mRNA was found in the most peripheral cell layer of the epithelial tumor islands. The presence of fibronectin mRNAs in the tumor cells of the central regions of the islands, as well as within occasional stromal cells, was also noted. Thus, two lines of evidence suggest that the epithelial tumor cells are predominantly responsible for the synthesis and deposition of fibronectin in basal cell carcinoma. The presence of fibronectin may explain the characteristic biologic behavior of basal cell carcinomas, including low degree of metastatic potential and local destructive nature of the tumors.

Topics: Autoradiography; Carcinoma, Basal Cell; Fibronectins; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Keratins; Nucleic Acid Hybridization; RNA, Messenger; Skin Neoplasms

Basal cell hyperplasia (BCH) is an uncommon proliferative lesion of the prostate gland. We studied ten cases of BCH, one case of an unusual adenoid basal cell tumor (ABT), and one case of a prostatic adenoid cystic carcinoma (ACC), using a panel of antibodies to define the histogenesis of these lesions. Monoclonal antibodies (MoAb) directed against a cytokeratin, which selectively stains basal cells (34 beta E12), and against muscle-specific actin, which stains myoepithelial cells (HHF35), were used. In addition, antibodies directed against prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), S-100 protein, and vimentin were used. In the normal prostate, epithelial cells reacted positively with 34 beta E12, PAP, and PSA, and negatively with the actin, S-100 protein, and vimentin antibodies. In BCH, positive staining was seen for 34 beta E12, PSA, and PAP, with no reactivity for actin, S-100 protein, and vimentin. In ABT and ACC, positive reactivity was demonstrated for all antibodies except actin and vimentin. These findings indicate that the basaloid cells of BCH, ABT, and ACC are derived from basal cells of the normal prostate gland and suggest a continuum among the three lesions. The presence of S-100 protein in ABT and ACC may be related to the lack of this antigen's specificity for myoepithelial cells. The absence of reactivity with the HHF35 MoAb supports our belief that the S-100 positivity does not necessarily indicate myoepithelial cell differentiation.

Topics: Acid Phosphatase; Actins; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Humans; Immunoenzyme Techniques; Keratins; Male; Prostatic Hyperplasia; Prostatic Neoplasms; S100 Proteins; Vimentin

Two cases of an esophageal carcinoma with an adenoid cystic differentiation are presented. The first was diagnosed histologically as typical adenoid cystic carcinoma, and the other as being a basal cell carcinoma with an adenoid cystic differentiation. We further investigated these tumors and normal esophageal specimens to determine their histological origin by immunohistochemical staining with either polyclonal or monoclonal antibodies to different classes of human keratin. It was found that both tumors were similar in their reactivities with the anti-keratin antibodies to basal cells of the surface squamous epithelia, but not to the cells composing the esophageal glands, suggesting that they were of basal cell origin.

Topics: Aged; Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Esophageal Neoplasms; Humans; Keratins; Male; Staining and Labeling

Basal cell carcinomas (BCCs) were cultured using an explant method and compared with normal cultured skin. Immunohistochemical staining revealed reduced beta 2 microglobulin uptake by BCCs in frozen section, but normal staining of the tumours in culture. In culture, fibronectin was detected on the cell surface of normal keratinocytes but not on BCCs. The above differences may explain some of the behaviour of BCCs in vivo.

Topics: Antigens, Neoplasm; beta 2-Microglobulin; Carcinoma, Basal Cell; Cell Division; Fibronectins; Humans; Immunoenzyme Techniques; Keratins; Skin Neoplasms; Tumor Cells, Cultured

Intermediate filament subunits are reliable markers of cytogenetic origin for both normal and neoplastic cells. Immunohistochemical localization of cytokeratin filaments offers a sensitive and specific means of identifying basal or reserve cells when studying histologic sections of skin biopsy specimens. We have applied this technique on eighteen cases in which unequivocal diagnosis or recurrent basal cell carcinoma could not be rendered by conventional histologic techniques. In three of the cases studied, microscopic islands of basal cell carcinoma could be demonstrated by positive staining with cytokeratin antibodies. In the remaining fifteen cases, the possibility of recurrent basal cell carcinoma could be conclusively eliminated on the basis of negative staining with this antibody. Immunolabeling with tissue specific cytokeratin antibodies by indirect immunofluorescent examination may thus constitute a reliable and relatively simple technique that may serve to establish a definitive diagnosis in equivocal cases of suspected recurrent basal cell carcinoma.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cytoskeleton; Diagnosis, Differential; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Neoplasm Recurrence, Local; Skin; Skin Neoplasms

Topics: Carcinoma, Basal Cell; Culture Media; Enzyme Induction; Enzyme Inhibitors; Epidermal Cells; Epidermis; Fibroblasts; Humans; Keratins; Microbial Collagenase; Skin Neoplasms; Tissue Extracts; Tissue Inhibitor of Metalloproteinases

The expression of certain classes of keratin is associated with cell maturation and differentiation. During cell transformation and tumor development, the cell specificity of intermediate filament, keratin, is largely conserved. Taking advantage of this, we utilized monoclonal antikeratin immunohistochemical techniques to examine basal and squamous cell carcinomas as they became deeply invasive. Dyskeratotic keratinocytes and keratin pearls in squamous cell carcinomas (SCCs) stain with antikeratin antisera to larger keratins (65-67 Kd). At the deep tumor margins, SCCs no longer express larger keratins but retain expression of 50, 58 Kd, which are markers of keratinocytes derived from stratified squamous epithelial cells. This selective loss of expression of keratin polypeptide markers of differentiation in SCC is associated with progressively more aggressive biologic behavior as the tumor invades deeper structures such as muscle and bone. Recurrent basal cell carcinoma (BCC) which was of the nodular type when first excised, shows features of morphea-like BCC and of aggressive growth patterns at the deep invasive margin. At these deep margins, some tumors express markers of keratinization (65-67 Kd). While tumor cells retain the specificity of the intermediate filament, keratin, the individual cells express products of differentiation as measured by keratin expression independently of their cytologic atypia. At the deeper invasive margin of the tumor, the neoplastic cells synthesize keratin proteins in an unpredictable fashion.

Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Invasiveness; Skin Neoplasms

Measurements of cell cycle kinetics using an immunoperoxidase method employing monoclonal anti-bromodeoxyuridine (BrdU) antibody were compared with an autoradiographic method using [3H]-thymidine. The methods were applied to epithelial cells grown from explants of normal skin and basal cell carcinoma (BCC), and to fibroblasts from normal skin, hypertrophic scar and keloid. In normal keratinocytes the number of peroxidase-positive cells was higher than the number incorporating [3H]-thymidine, because of the presence of labelled cells in the centre of the explants in the former. The epithelial cells from BCC gave a mean (+/- SD) of 4.9 +/- 1.2% peroxidase-positive cells, while no cells were labelled with [3H]-thymidine. In dermal fibroblasts from normal skin and hypertrophic scar the percentages of peroxidase-positive cells did not differ significantly from the [3H]-thymidine labelling indices. The immunological method has advantages over [3H]-thymidine autoradiography in that it avoids radioactive material and the proportion of cells labelled by the two methods is the same.

Topics: Antibodies, Monoclonal; Autoradiography; Bromodeoxyuridine; Carcinoma, Basal Cell; Cell Division; Culture Techniques; Epidermis; Fibroblasts; Humans; Immunoenzyme Techniques; Keratins; Kinetics; Skin Neoplasms

164 odontogenic keratocysts from 60 patients with the basal cell naevus syndrome were compared with a similar number of single keratocysts matched for age and site. Significant differences between the two groups were found in the numbers of satellite cysts, solid islands of epithelial proliferation and odontogenic rests within the capsule, and in the numbers of mitotic figures in the epithelium lining the main cavity. An index of activity derived from these parameters suggests a greater growth potential in syndrome cysts; in addition, the patterns of association of the features support the theory that the odontogenic rests give rise to satellite cysts.

Topics: Adolescent; Adult; Aged; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Cell Division; Child; Female; Humans; Keratins; Male; Mandibular Neoplasms; Maxillary Neoplasms; Middle Aged; Odontogenic Cysts

Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Fluorescent Antibody Technique; Humans; Keratins; Microscopy, Electron; Skin; Skin Neoplasms

Topics: Adult; Antibodies, Neoplasm; Carcinoma, Basal Cell; Female; Humans; Keratins; Skin Neoplasms

Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Skin Neoplasms

The reactivity of a monoclonal antibody against human T lymphotropic retrovirus (antibody 12/1-2, recognising the HTLV-1 p19 internal core viral protein) with benign and malignant cutaneous biopsy specimens was examined and compared with results obtained on normal skin, on various other human cells and tissues, and on immunoblotted extracts of tonsil squamous epithelium. In keeping with previous studies, 12/1-2 labelled a proportion of the thymic epithelial stroma and the entire layer of basal cells in stratified non-keratinized and keratinized epithelium. Furthermore, antibody 12/1-2 reacted with basal cell carcinomas and showed an essentially identical staining pattern in normal skin, cutaneous T cell lymphomas, and a range of benign dermatoses. The dot blot preparations showed that 12/1-2 recognised an antigen associated with keratin intermediate filaments. These data indicate that antibody 12/1-2 forms a useful marker for subsets of epithelial cells, which presumably participate in T cell education, and that a range of cutaneous disorders of widely different aetiology show no abnormalities in epithelial expression of this antigen.

Topics: Antibodies, Monoclonal; Antibodies, Viral; Antigens; Carcinoma, Basal Cell; Deltaretrovirus; Epithelium; Humans; Keratins; Lymphoma; Palatine Tonsil; Skin; Skin Diseases; Skin Neoplasms; T-Lymphocytes; Thymus Gland

Colloid keratosis is characterized by homogeneous eosinophilic masses of variable size and number within the upper layers of squamous epithelia, including epidermis. It has been observed as the characteristic feature of many onychoses and inflammatory conditions of oral epithelium, and as an incidental finding in neoplastic and nonneoplastic lesions in the skin and respiratory tract. Its nature remains obscure, but knowledge at present suggests that it may represent a disorder of an early phase of keratinization. Current evidence supports the hypothesis that colloid keratosis represents a nonspecific cellular reaction pattern of squamous epithelium.

Topics: Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Colloids; Eosinophilia; Epithelium; Female; Humans; Keratins; Keratosis; Male; Middle Aged; Necrosis; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling

Different tumours of the head and neck were analysed by immunohistochemistry. The distribution pattern of several intermediate filaments was studied. Keratin filaments were typical of carcinomas, whereas vimentin filaments were typical of mesenchymal tumours of different origin. The advances of this new technique of "tumour typing" are discussed.

Topics: Carcinoma, Basal Cell; Cytoskeleton; Diagnosis, Differential; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Lymphoma; Melanoma; Mouth Neoplasms; Nasopharyngeal Neoplasms; Neuroma, Acoustic; Oropharyngeal Neoplasms; Tonsillar Neoplasms; Vimentin

Involucrin has been recognized recently as a marker of terminal differentiation of squamous epithelial cells and also as a useful marker for keratinization; its expression in epithelial tumors of oral and pharyngeal mucosa and skin was examined. Involucrin in normal oral mucosa and skin was restricted to the granular and upper spinous layers and was absent in the basal layer. Hyperkeratosis was characterized by strong positive staining for involucrum in spinous and granular cell layers. A similar pattern was noted in seborrheic keratosis and verruca vulgaris. Condyloma acuminatum specimens revealed slight staining, whereas Paget cells were negative. Calcifying epitheliomas of Malherbe were usually unreactive. Papillomas exhibited the regular distribution of involucrin, as found in normal squamous epithelium. Basal cell carcinomas were generally negative, whereas squamous cell carcinomas showed an irregular distribution of involucrin. Immunohistochemical staining for involucrin may be useful for identification of keratinizing cells in epithelial tumor foci, just as is the use of monoclonal antibody to keratin KL1.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Papilloma; Pharyngeal Neoplasms; Protein Precursors; Skin Diseases; Skin Neoplasms; Staining and Labeling

Topics: Antibodies; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins

Xenografting into nude mice forms a system for analysis of human tissues under experimental conditions. In this study, normal skin samples and basal cell carcinomas were investigated, prior to and after transplantation, using immunofluorescence methods with antibodies against keratins, laminin, and collagen type IV. Three groups of transplants were studied: intact tissue samples, human epithelium (either normal or neoplastic) recombined with normal human dermis and, human epithelium recombined with normal mouse dermis. Transplants recovered after 3 weeks showed the following characteristics. The xenograft system was satisfactory in terms of host survival and rate of successful tissue recovery except for recombinants between human epithelium and mouse dermis. Intact and recombined samples of normal skin retained their preexisting patterns of architecture, cytodifferentiation, and basement membrane staining. Solid nonfibrosing basal cell carcinomas showed altered architecture and differentiation of both the epithelium and the basement membrane zone after transplantation: the solid tumor pattern changed towards spreading of tumor cells, a more squamous differentiation pattern was apparent and was confirmed by reactivity with antibodies against large keratins. Discontinuities of the basement membrane zone were detected with antibodies against laminin and collagen type IV. These changes were seen in both intact and recombined tumor transplants.

Topics: Animals; Basement Membrane; Carcinoma, Basal Cell; Collagen; Fluorescent Antibody Technique; Humans; Keratins; Laminin; Mice; Mice, Nude; Neoplasm Transplantation; Skin; Skin Neoplasms

One hundred cutaneous tumors were investigated immunohistopathologically for the expression of intermediate filament (IF) proteins. Epithelial tumors, such as basocellular and squamous cell carcinomas, cutaneous adnexal tumors, and metastatic carcinomas showed keratin positivity in a varying number of tumor cells with two keratin antibodies with different specificities. Neoplastic cells of fibrohistiocytic tumors, pigmented nevi, melanomas, hemangiomas, glomus tumors, and lymphomas were positive for vimentin, but not for keratin or desmin. Cutaneous leiomyomas and leiomyosarcomas, on the other hand, were positive for desmin. The results show that the typing of IFs enables the differential diagnosis between carcinomas and sarcomas or melanomas, epidermal appendage tumors, and mesenchymal tumors, and between fibrohistiocytic and leiomyocytic tumors, and therefore are of diagnostic value in histopathologic problems of the skin.

Topics: Adenocarcinoma; Adenoma, Sweat Gland; Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Desmin; Diagnosis, Differential; Fluorescent Antibody Technique; Hemangioma; Histiocytoma, Benign Fibrous; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Leiomyoma; Melanoma; Neoplasm Metastasis; Nevus, Pigmented; Skin Neoplasms; Vimentin

The connective tissue adjacent to basal cell carcinomas (BCC) is frequently abnormal and contains increased numbers of fibroblasts and increased extractable collagenase. To determine whether BCC could produce these alterations by releasing mediators that regulated fibroblast function, we established BCC in culture and tested the ability of their culture supernatants to alter fibroblast proliferation and production of collagenase. Using tissue culture plates coated with type IV collagen and containing x-irradiated 3T3 feeder cells, we established epithelial colonies from 47% of the BCC cultured. The BCC-derived colonies differed from normal epidermal cell colonies in their morphology, growth rate, and keratin production. Culture supernatants from 4 out of 5 confluent BCC-derived colonies contained factors that stimulated fibroblasts to proliferate and release collagenase. These findings show that BCC-derived epidermal cell colonies release mediators which alter fibroblast functions and suggest that some of the connective tissue changes associated with BCC in vivo are the result of BCC-fibroblast interactions.

Topics: Aged; Biological Products; Carcinoma, Basal Cell; Cell Division; Cells, Cultured; Cytokines; Fibroblasts; Humans; Keratins; Microbial Collagenase; Middle Aged

Microphotometric measurements of fast reacting protein thiols (PSHr) and proteins were performed on freshly frozen sections of samples from normal skin (26 cases as controls) and from 45 basal cell epitheliomas (basalioma; BCE). The intensity of the staining (E/micron2) for both proteins and PSHr was significantly higher in normal epidermis than in the adjacent dermis. The values of QE (quotient of values observed in the epidermis divided by those observed in the dermis) were calculated to be 3.48 for proteins (QE, Prot) and 4.62 for PSHr (QE, PSHr). In cases of BCE, significantly lower QE values were found: QE, Prot = 2.16 and QE, PSHr = 1.72. The decrease of QE, PSHr was due to a decrease in the staining intensity observed in the BCEs, whereas practically no changes occurred in the adjacent dermis. The decrease of QE, Prot was mainly caused by a decrease in the staining intensity in the BCE (by 68%) as well as in the adjacent dermis (by 36%). By dividing the mean extinction value (E/micron2) for PSHr by the E/micron2 for proteins, a new quotient, PSHr/Prot, is obtained which can serve as a quantitative measure of the content of the tissue proteins of PSHr. The proteins of normal epidermis contained more PSHr than dermal proteins. The proteins of BCEs also contained more PSHr than those of the adjacent dermis, but the PSHr/Prot values of both tissues were 1.5 to 1.6 times greater than the corresponding values for normal epidermis and dermis, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Carcinoma, Basal Cell; Female; Humans; Keratins; Male; Proteins; Skin; Skin Neoplasms; Staining and Labeling; Sulfhydryl Compounds

Twenty-nine cases of basal cell carcinoma were studied with immunoperoxidase techniques for the detection of carcinoembryonic antigen. Results presented in the text would indicate that a high percentage of basal cell carcinomas have sweat gland histogenetic origins and that this is independent of its morphologic features. The use of immunohistochemical techniques in the detection of biological markers demonstrates once again their value not only in identifying a disease but also in determining its histogenetic origins.

Topics: Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Basal Cell; Cell Differentiation; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Skin Neoplasms; Sweat Gland Neoplasms

A murine hybridoma secreting an IgM monoclonal antibody (KL3) was produced by cell fusion of mouse myeloma cells with spleen cells from mice immunized with human epidermal keratins. On normal human epidermis KL3 stained the intercellular spaces from the stratum germinatum to the stratum granulosum with a fluorescence intensity increasing from the basal layer to the upper layers. Basal cells were not stained on the side facing the basement membrane. About 90% of free keratinocytes isolated after trypsinization were labelled by KL3 in a punctate staining. Immunoelectron microscopy allowed us to show that the antigen recognized by KL3 was exclusively localized on the keratinocyte membrane especially in the desmosomal plaques. KL3 reactivity was not modified by preincubation of skin sections with lectins showing a selective intercellular labelling of upper layers of epidermis or pemphigus antisera, nor by adsorption of the antibody on NP40 soluble proteins of the epidermis. Though KL3 reactivity was completely abolished after adsorption of purified keratins, no immunological reactivity of KL3 was detected with epidermal keratin polypeptides blotted on nitrocellulose paper. In psoriatic epidemis and epidermal tumors KL3 reactivity was drastically modified. These results suggest that KL3 recognized a keratinocyte membrane antigen implied in the epidermal differentiation process.

Topics: Animals; Antibodies, Monoclonal; Antigens, Surface; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Membrane; Epidermal Cells; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Macaca fascicularis; Mice; Psoriasis; Rabbits; Skin; Skin Diseases; Skin Neoplasms; Warts

Seventy-six cases of tumorlike and neoplastic lesions from epidermis and oral epithelium were analyzed by a histochemical technique for the demonstration of keratin. Formalin-fixed paraffin sections were reacted with rabbit antihuman keratin antiserum (dilution of 1:40). The types of distribution of keratin in cells of lesions were classified into five categories: (1) regional, as found in normal squamous epithelia and benign hyperkeratinized lesions, and papilloma, and keratinized squamous cell carcinoma; (2) total, as seen in intensely keratinized lesions, such as verruca vulgaris and highly keratinized squamous cell carcinoma; (3) negative, as displayed by basal cell carcinoma; (4) scattered, as in the most poorly differentiated squamous cell carcinomas; and (5) mixed cellular, as found in both poorly and moderately differentiated squamous cell carcinomas.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dermatitis, Seborrheic; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Keratosis; Lectins; Mouth Neoplasms; Papilloma; Protein Binding; Skin Neoplasms; Warts

Familial odontogenic keratocysts are described in this report. The Case 1 patient, who has 3 sisters, developed odontogenic keratocysts. The 2 younger sisters (Cases 2 and 3) also had odontogenic keratocysts, although the elder sister did not have any odontogenic cysts. The father of the patients had a history of removal of a jaw cyst, and the mother was found later to have malignant ameloblastoma. Besides the odontogenic keratocysts, the Case 1 patient had basal cell nevus, prominent frontal process, and ocular hypertelorism; the Case 2 patient had prominent frontal process; the Case 3 patient had prominent frontal process, ocular hypertelorism, and squint. All 3 sisters are suspected of being patients with the basal cell nevus syndrome. The Japanese dental literature concerning the basal cell nevus syndrome is reviewed.

Topics: Adolescent; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Child; Diagnosis, Differential; Female; Humans; Keratins; Odontogenic Cysts

Keratin composition has been widely used as a biochemical marker of differentiation in normal epithelia, cell culture systems and tumours of epithelial tissues. We have been developing a model system for the study of human squamous epithelial cell differentiation, and among a panel of monoclonal antibodies we have generated for analysing this system are two antibodies recognizing subsets of epidermal keratins. The two antibodies, designated LICR-LON-16a and LICR-LON-29b, were raised to the human squamous carcinoma cell line LICR-LON-HN-5, and we describe here their biochemical and immunocytochemical characterization. Antibody 16a reacts with only epidermal basal cells in normal human skin and shows specificity for the 45 and 46 kdalton keratins. Antibody 29b stains all living layers of the epidermis, and reacts with a broad range of ketain polypeptides, (45-56 kdaltons) in immunoblotting analyses. We have investigated the alterations of cellular staining that occur in chronic hyperproliferative skin diseases and carcinomas and compared this with the staining of multilayered cultures of normal keratinocytes and the HN-5 cell line. We show that in squamous cell carcinomas and in HN-5 cell xenografts 16a and 29b stain only the well-differentiated cell types. Furthermore we found that the basal cell specificity of 16a was lost in all of the hyperproliferative skin lesions examined including psoriasis and eczema. This transition to suprabasal staining pattern was also seen in the cultures of normal keratinocytes and HN-5 cells. We conclude that aberrant keratin synthesis or abnormal post-translational processing of keratins associated with an increased rate of cell turnover could account for the altered expression of the epitope recognized by antibody 16a.

Topics: Antibodies, Monoclonal; Antibody Specificity; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Epitopes; Humans; Keratins; Skin; Skin Neoplasms

In normal skin, cytokeratin polypeptides are expressed in different cell-type-specific patterns, in the keratinocytes of the different epidermal cell strata as well as in different lateral epithelial domains. Using light microscopically controlled microdissection of defined regions from frozen sections of biopsies, we have prepared cytoskeletons of various benign and malignant keratinocyte-derived tumors of human skin and analyzed their cytokeratin polypeptide patterns by two-dimensional gel electrophoresis. Premalignant fibroepitheliomas and basal cell epitheliomas display a relatively simple cytokeratin pattern (cytokeratins nos. 5, 14, 15, and 17). Pseudocarcinomatous hyperplasia, some squamous cell carcinomas, and a certain subtype of condylomata acuminata present a hair-follicle-like pattern (nos. 5, 6, 14, 16, 17). In addition to these components, variable, mostly low amounts of cytokeratins nos. 1 (Mr 68,000), and 11 are detected in most squamous cell carcinomas, in keratoacanthomas, verruca vulgaris, and another type of condylomata acuminata. In molluscum contagiosum, verruca plana, solar keratosis, and seborrheic keratosis, the cytokeratin expression is shifted more towards the normal epidermal pattern (polypeptides nos. 1, 2, 5, 10, 11, 14, 15 and traces of nos. 6 and 16 in the latter two tumors). No tumor-specific cytokeratins have been found. We conclude that keratinocyte-derived skin tumors contain various combinations of cytokeratins of the subset typical for normal keratinocytes of skin, but no cytokeratins typical for internal, simple epithelia. Different groups of tumors can be distinguished by their specific cytokeratin patterns. Possible applications of cytokeratin typing in clinical diagnosis are discussed.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Condylomata Acuminata; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Keratoacanthoma; Keratosis; Molecular Weight; Molluscum Contagiosum; Papilloma; Peptides; Skin; Skin Neoplasms; Warts

The expression of cellular glycoconjugates and cytokeratin polypeptides in 8 basal cell carcinomas (BCC) was studied using fluorochrome-coupled lectins and different keratin-antibodies. Peanut agglutinin and Wistaria floribunda agglutinin, binding to all layers of normal human epidermis, also stained all cells in the basal cell carcinomas. Dolichos biflorus agglutinin, which in normal epidermis binds only to the basal cells, gave a mottled staining pattern in most of the tumors. Instead, Ulex europaeus I agglutinin and soybean agglutinin, which in normal epidermis only bind to the spinous and granular cell layers, did not stain tumor cells in basal cell carcinomas. Rabbit antibodies to human 43-50kD epidermal keratin polypeptides and 2 monoclonal cytokeratin antibodies, PKK1 reacting only with follicular epithelium, and PKK2 reacting also with the basal epidermal cells, brightly stained all cells of the basal cell carcinomas studied, whereas antibodies to human 60-67kD epidermal keratin polypeptides did not bind to the carcinoma cells. The results suggest that the cells in basal cell carcinomas resemble epidermal basal cells both by their glycoconjugate pattern and keratin expression. However, the tumor cells also express cytokeratins, which can be found only in the follicular epithelium, but not in normal interfollicular epidermis.

Topics: Adult; Aged; Antibodies; Carcinoma, Basal Cell; Cell Differentiation; Fluorescent Dyes; Humans; Keratins; Lectins; Middle Aged; Skin Neoplasms

Profiles of immunohistochemical staining for different molecular weight keratin proteins (45, 46, 55, and 63 kilodalton (kd] were evaluated in basal and squamous cell carcinomas of the skin and surrounding epidermis. Basal cell carcinomas predominantly stained with antisera to low molecular weight keratins (45 and 46 kd). Staining with antisera to higher molecular weight keratins (55 and 63 kd) was focal and restricted to areas of squamous differentiation. Invasive squamous cell carcinomas in addition to staining with antisera to low molecular weight keratins (45 and 46 kd) showed diffuse staining for 55-kd keratin and foci of staining for 63-kd keratin most prominent in keratinized regions of the tumors. In situ squamous cell carcinomas (Bowen's disease) differed from invasive squamous cell carcinoma in showing increased staining for high molecular weight keratin (63 kd). Abnormal keratin profiles were identified adjacent to and overlying basal and squamous cell carcinomas, with antisera to low molecular weight keratins (45 and 46 kd) staining all layers of the epidermis, and decreased intensity of staining for high molecular weight keratin (63 kd). Keratin profiles may help define abnormal squamous maturation in epidermis adjacent to tumors. Immunohistochemical staining for different molecular weight keratin proteins may also be helpful in the differential diagnosis of skin lesions.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Humans; Immunoenzyme Techniques; Keratins; Molecular Weight; Skin; Skin Neoplasms

Microscopically controlled surgery (Mohs' surgery) is a widely accepted technique because it provides total extirpation of skin tumors with maximum conservation of tissue. However, in poorly differentiated tumors it is often difficult microscopically to recognize individual tumor cells in the midst of an inflammatory cell infiltrate, in fibrotic tissue, in connective tissue around blood vessels, in nerve sheaths, and in fascial planes. We have developed techniques to differentiate tumor cells, derived from the epidermis, from the normal nonkeratinizing tissue of mesodermal origin or the inflammatory cell infiltrate. In frozen sections, indirect immunofluorescence techniques with polyclonal antibodies to fibrous keratin allowed rapid identification of tumor cells of basal and squamous cell carcinoma. Immunoperoxidase staining proved to be a remarkably sensitive method for the identification of such carcinoma cells in both frozen and paraffin-embedded sections. When used in combination with the precise mapping techniques of Mohs' surgery, these reliable and specific stains permitted greater accuracy in assessing the total resection of an invasive tumor.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Neoplasm; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermis; Fluorescent Antibody Technique; Frozen Sections; Humans; Immunoenzyme Techniques; Keratins; Rabbits; Skin Neoplasms

The authors have used 5 different monoclonal antikeratin antibodies to study the antigenic profiles of cytoid bodies and skin-limited amyloids. Monoclonal antibodies AE1 (which stains the basal cell layer in normal human epidermis), AE2 (suprabasal layers), AE3 (whole epidermis), EKH4 (lower 2-3 layers), and EKH1 (recognizes all classes of intermediate filaments) were used to stain frozen skin sections by the indirect immunofluorescent or indirect immunoperoxidase technique. Cytoid bodies in lichen planus (LP) and discoid lupus erythematosus (DLE) were strongly stained with AE1, AE3, EKH4, and EKH1 antibodies but were negative with AE2. In contrast, amyloids in lichen amyloidosus and macular amyloidosis were stained strongly with EKH4 but only weakly or not at all with AE1, AE2, AE3, and EKH1. Amyloid associated with epithelial tumors showed closer immunologic profiles to cytoid body. These findings suggest that epidermal keratins are the major precursor substance of skin-limited amyloids as well as cytoid bodies in LP and DLE. Sequential changes in antigenic profiles from basal cells to amyloids through cytoid bodies further suggest that cytoid bodies may represent one of the precursor substances of skin-limited amyloids.

Topics: Amyloid; Amyloidosis; Antibodies, Monoclonal; Carcinoma, Basal Cell; Fluorescent Antibody Technique; Humans; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Skin Diseases; Skin Neoplasms; Staining and Labeling

Involucrin is a precursor of cross-linked protein of human stratum corneum, and its appearance in the upper layers of the epidermis is a function of the normal differentiation of the keratinocyte. Cases of basal cell and squamous cell carcinoma were evaluated for the presence of involucrin using immunoperoxidase techniques on paraffin sections. Basal cell carcinomas were negative for involucrin with staining restricted to squamous horn cysts, while squamous cell carcinomas stained strongly, particularly in large keratinized cells. Cases of squamous cell carcinoma in situ (Bowen's disease) revealed increased staining for involucrin with staining of dyskeratotic cells at all levels in the epithelium. Abnormal patterns of staining were also noted in non-neoplastic epidermis adjacent to carcinomas. Immunohistochemical staining for involucrin identifying abnormal or premature keratinization is a sensitive marker for dyskeratosis in squamous epithelia and may have applications in the histopathologic evaluation of skin specimens.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermis; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Protein Precursors; Skin Neoplasms

The presence of intracellular keratin was examined in 230 human neoplasms using indirect immunofluorescence on fresh frozen, acetone-fixed sections. The use of antikeratin antibodies raised in rabbits against human callus and purified by affinity chromatography proved to be a rapid, sensitive, and reliable method of demonstrating keratin. Epithelial tissues and epithelial-derived neoplasms were found to contain keratin, whereas tissues and neoplasms of mesenchymal, lymphoreticular, or neural crest origin did not contain intracellular keratin. This technic is a useful adjunct for the surgical pathologist in the diagnosis of poorly differentiated neoplasms. Its application either confirmed, modified, or in several instances, changed the original light microscopic impression. The modified or changed diagnoses were confirmed by transmission electron microscopy.

Topics: Adult; Aged; Antibodies; Breast Neoplasms; Carcinoma, Basal Cell; Female; Fluorescent Antibody Technique; Humans; Keratins; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Middle Aged; Neoplasms; Skin Neoplasms; Thymoma

Recent advances in the biology of the epidermis increase our understanding of skin cancer. Epidermal tissue culture demonstrates that cells from epidermal malignancies retain their malignant characteristics. Some epidermal tumors contain a low molecular weight keratin as a major structural protein; a low molecular weight keratin is a characteristic of fetal epidermis as well. Certain epidermal cell-surface antigens, such as the pemphigus antigen, may be absent in skin cancers. A population of long-lived skin cells may be the site for genetic alterations that eventually produces skin cancers. A population of basal "dark" cells is increased after treatment with tumor promoting agents such as phorbol esters. Two-stage (initiation, promotion) epidermal carcinogenesis can now be studied in tissue culture. Several components of the complex multilayered basement membrane zone are produced by epidermal cells. Malignancies of epidermal cells may extend beyond the basement membrane zone by disordered synthesis of the zone or by producing enzymes including collagenases that alter the zone.

Topics: Animals; Antigens, Surface; Basement Membrane; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cells, Cultured; Epidermal Cells; Epidermis; Humans; Keratins; Langerhans Cells; Mice; Skin Neoplasms

The immunofluorescence technique using antisera against human plantar stratum corneum fibrous protein (total keratin) and 64K M.W. keratin subunit isolated from total keratin by SDS polyacrylamide gel electrophoresis (PAGE) was used to examine epidermal keratinization in some skin disorders. In normal skin, total keratin was distributed throughout the epidermis, while 64K keratin was localized at the suprabasal layers. In the case of squamous cell carcinoma (SCC), the tumor cells were uniformly stained positive with total keratin antiserum, whereas diminished or negatively stained cells were observed with 64K keratin antiserum (64K antiserum), suggesting that the tumor included cells in various stages of differentiation. In basal cell epithelioma (BCE), most of the tumor cells were negatively stained with 64K antiserum being consistent with the histologic observation that BCE is originated from the basal cells. However, some of the tumor cells were stained positive with 64K antiserum, indicating that individual cell keratinization might occur in BCE. In lichen planus, an inflammatory disease demonstrating so-called lichnoid tissue reaction, positively stained colloid bodies in the upper dermis were observed either with total keratin antiserum or with 64K antiserum. It was suggested that colloid bodies resulted from individual keratinization of damaged keratinocytes during inflammation.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermis; Fluorescent Antibody Technique; Humans; Keratins; Lichen Planus; Skin Neoplasms

A rabbit antiserum prepared against human keratins isolated from calluses was applied to sections of 108 neoplasms using indirect immunofluorescence and immunoperoxidase technics. The vast majority of epithelial neoplasms were strongly positive for keratin-type proteins, even in the absence of obvious keratinization or squamous differentiation as revealed by light microscopy. This keratin-positivity was invariably correlated with the identification of intermediate-sized filaments arranged in loose or dense bundles in the cytoplasm of neoplastic epithelial cells. Keratin-negative neoplasms included nevi, malignant melanomas, carcinoid tumors, malignant lymphomas, and a variety of connective-tissue tumors. Immunologic identification of keratin-type proteins was particularly helpful in establishing the epithelial nature of "undifferentiated" malignant tumors, including oat cell carcinomas.

Topics: Adenocarcinoma; Animals; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Humans; Immunoenzyme Techniques; Keratins; Rabbits; Skin Neoplasms; Urinary Bladder Neoplasms

Cytokeratin polypeptides of human epidermis, of epithelia microdissected from various zones of the pilosebaceous tract (outer root-sheath of hair follicle, sebaceous gland), and of eccrine sweat-glands have been separated by one- and two-dimensional gel electrophoresis and characterized by binding of cytokeratin antibodies and by peptide mapping. The epithelium of the pilosebaceous tract has three major keratin polypeptides in common with interfollicular epidermis (two basic components of mol wts 58,000 and 56,000 and one acidic polypeptide of mol wt 50,000); however, it lacks basic keratin polypeptides in the mol wt range of 64,000-68,000 and two acidic keratin-polypeptides of mol wts 56,000 and 56,500 and contains an additional characteristic acidic cytokeratin of mol wt 46,000. Another cytokeratin polypeptide of mol wt 48,000 that is prominent in hair-follicle epithelium is also found in nonfollicular epidermis of foot sole. Both epidermis and pilosebaceous tract are different from eccrine sweat-gland epithelium, which also contains two major cytokeratins of mol wts 52,500 and 54,000 (isoelectric at pH 5.8-6.1) and a more acidic cytokeratin of mol wt 40,000. A striking similarity between the cytokeratins of human basal-cell epitheliomas and those of the pilosebaceous tract has been found: all three major cytokeratins (mol wts 58,000; 50,000; 46,000) of the tumor cells are also expressed in hair-follicle epithelium. The cytokeratin of mol wt 46,000, which is the most prominent acidic cytokeratin in this tumor, is related, by immunological and peptide map criteria, to the acidic keratin-polypeptides of mol wts 48,000 and 50,000, but represents a distinct keratin that is also found in other human tumor cells such as in solid adamantinomas and in cultured HeLa cells. The results show that the various epithelia present in skin, albeit in physical and ontogenic continuity, can be distinguished by their specific cytokeratin-polypeptide patterns and that the cytoskeleton of basal-cell epitheliomas is related to that of cells of the pilosebaceous tract.

Topics: Carcinoma, Basal Cell; Epidermis; Epithelial Cells; Epithelium; Hair; Humans; Intermediate Filament Proteins; Isoelectric Point; Keratins; Molecular Weight; Neoplasm Proteins; Peptide Fragments; Sweat Glands

Topics: Carcinoma, Basal Cell; Diagnosis, Differential; Humans; Keratins; Leukoplakia, Oral; Lip Neoplasms; Male; Middle Aged

The nature of epithelial cell cytokeratins from epidermal basal cell carcinomas (BCC) (8 cases) and squamous cell carcinomas (SCC) (5 cases) was investigated by biochemical and immunological analysis. Cytokeratin proteins were extracted with high salt buffer and triton X 100 and were comparatively analyzed by SDS (sodium dodecyl sulphate) polyacrylamide gel electrophoresis. Both types of tumor showed either an absence or a very low amount (5% of the total protein) of the major protein band (MW 67000) present in normal human epidermis. This correlated well with results of immunolabelling showing that 67000 keratin antisera, only reacted with some dyskeratotic cells in sections of these tumors. Gel electrophoresis showed in BCC and SCC, three distinct groups of predominant polypeptide bands of apparent relative MW: (1) 60-62000 (2) 54-56000 and (3) 49000, representing respectively about 43.0%, 31.0% and 20.4% of the total proteins. Antibodies raised in animals against polypeptide bands C1 (MW 62000), C2 (MW 56000) and C3 (MW 49000) from SCC, strongly labelled (indirect immunofluorescence) all malignant cells present in the 2 kinds of tumors. These antisera showed a preferential reaction with the basal epithelial cells, in sections of human and animal epidermis and mucosa thus, suggesting numerous common antigenic determinants between epithelial cells from diverse origins. On the other hand, strong differences between mucosal and epidermal upper layers were noted with C1, C2, C3 and 67000 antisera. These results are further evidence for the existence of different pathways of keratinization in epidermis and mucosa.

Topics: Animals; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epithelium; Fluorescent Antibody Technique; HeLa Cells; Humans; Intestines; Keratins; Mouth Mucosa; Rabbits; Rats; Skin

Antibodies to human and bovine epidermal prekeratin and antibodies to mouse liver cytokeratin component D (Mr 49 000) have been applied in indirect immunofluorescence microscopy on sections of human tumors of mammary gland and liver. In non-neoplastic mammary gland all epithelial cells were stained with these antibodies. In pre-invasive and invasive ductal and lobular carcinomas a cell population was observed which was not significantly stained with antibodies to epidermal prekeratin but did strongly react with antibodies to liver cytokeratin D. In the liver, the antibodies to epidermal prekeratin as well as those directed against liver cytokeratin D strongly decorated bile duct epithelia. In contrast, significant staining of the hepatocytes was only achieved with antibodies to liver cytokeratin D. This different staining reaction was maintained in liver tumors of hepatocellular and cholangiocellular origin. Antibodies to vimentin stained mesenchymal cells and tumors of mesenchymal derivation but reacted not significantly with any of the epithelial and carcinoma cells examined. The difference is of practical importance for the discrimination between anaplastic carcinomas and sarcomas of unknown origin. Cytokeratin could also be detected by antibody staining using the peroxidase-antiperoxidase (PAP) technique in formaldehyde-fixed and paraffin-embedded material of skin, gastrointestinal, respiratory, urinary and genital tract as well as various glands, liver and kidney. Examples of positive reactions were shown in a squamous cell carcinoma, a basalioma and a pleomorphic adenoma of the parotis. It is concluded that the immunohistochemical analysis of intermediate filament proteins has diagnostic potential in clinical pathology and may help to elucidate histogenesis and differentiation of tumors and possibly also prognosis of tumor growth. It is further suggested to use antibodies recognizing different subsets of proteins of the cytokeratin family in order to distinguish between different types of carcinomas.

Topics: Adenoma, Pleomorphic; Breast Neoplasms; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Liver Neoplasms; Parotid Neoplasms; Protein Precursors; Sarcoma; Skin Neoplasms

Antibodies against different fractions of keratins can be helpful in various fields of special pathology. Antibodies against "small" and "large" keratins permit to evaluate epithelial maturation in skin and oral mucosa. In addition, disturbances of keratinization during inflammatory processes and malignant transformation can be analyzed. The main application of antibodies against the entire fractions of keratins is the detection of the epithelial nature of a neoplasm. By this tool, particular problems in surgical pathology concerning differential diagnosis can be handled in an easier way. Among the different tissues and their neoplasms, examples of the analysis of thymus tumours and salivary gland tumours are presented. Immunoreactivity with keratin antibodies depends crucially on tissue processing. In the normal diagnostic procedure, good results are regularly obtained if cryostat or Bouin-fixed paraffin-embedded sections are used.

Topics: Adenoma; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoskeleton; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Parakeratosis; Salivary Gland Neoplasms; Salivary Glands; Skin; Skin Neoplasms; Thymus Gland; Thymus Neoplasms

Prekeratin was reduced in human skin malignancies comparing Bowen's carcinoma (BC), basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) with normal epidermis. This observation correlated with ultrastructural appearance and frequency of tonofilaments. Gel electrophoresis of tumor extracts revealed the decrease or loss of larger prekeratin peptides (65 to 68 K daltons) prominent in the epidermis. Biopsies, particularly from BC, resembled normal keratinocytes in culture with respect to their prekeratin patterns (48 to 61 K daltons). The pattern was most different, and prekeratin lowest, in SCC and derived cultures. In BCC-cultures, however, prekeratin (almost identical to keratinocytes) and filament formation significantly exceeded the respective tumor levels.

Topics: Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Line; Epidermis; Humans; Keratins; Protein Precursors; Skin Neoplasms

Anti-keratin polypeptide sera (K.P.S) were obtained by immunizing guinea pigs with fibrous proteins from stratum corneum, which were acquired from normal human epidermis by m eans of S.D.S. polyacrylamide gel electrophoresis. After absorption with red blood cells and liver powder the sera were tested by indirect immunofluorescence technique on different substrates. Antibodies against polypeptides P1 and P2 of M.W. 67,000 and 62,000 dalton, respectively, were directed toward cytoplasmic Ag of keratinocytes of spinous and graunular layer of normal human and rabbit epidermis. No labeling could be detected in the basal cell layer. This finding is in favor of various differentiation stages of the keratinizing cells. P3 of M.W. 53,000 dalton induced low titre anibodies which labelled the whole epidermis, including the basal cell layer. The fourth polypeptide of M.W. 49,000 dalton seemed not to be immunogenic in such experiences. In tumors, such as basal cell carcinom,a squamous cell carcinoma, and warts, the expression of keratin antigens is markedly diminished. No analogy could be drawn between experimental keratin polypeptide antibodies and the human epidermal cytoplasmic antibodies which were detected in some patient sera.

Topics: Animals; Antibody Formation; Antibody Specificity; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoplasm; Epidermis; Female; Fluorescent Antibody Technique; Guinea Pigs; Humans; Keratins; Peptides; Rabbits; Skin; Skin Neoplasms; Warts

The mixture at equal volumes of a 0.1 p. 100 solution of rhodamine B in distilled water and of a 0.25 p. 100 solution of toluidine blue in Walpole's pH 4.4 buffer dyes each pilar sheath differently. At the level of the medulla, the granules fix rhodamine B, so do the cortical cells at the level of the keratogenic zone. Once they are keratinized, however, cortical cells remain colorless. Concerning the cells of the inner root sheath, on the other hand, their trichohyaline granules are dyed by rhodamine B, whereas the keratinized cells turn dark blue under the effect of toluidine blue. The trichilemmal keratin both of the isthmus of the anagen hair and of the follicular sac becomes light red. This technique, which can be easily applied to the trichogram, allows us to identify more or less mature pilar anlages in in adnexal tumors, to differentiate keratinizing cysts and to trace various pathological keratins. Thanks to a chemical study, it was shown that the mixture rhodamine B-toluidine blue is only a mechanical mixture which works through its acide-bases properties.

Topics: Carcinoma, Basal Cell; Cysts; Diagnosis, Differential; Epidermis; Hair; Hair Diseases; Histocytochemistry; Humans; Keratins; Rhodamines; Skin Neoplasms; Xanthenes

Topics: Amyloid; Amyloidosis; Carcinoma, Basal Cell; Epidermis; Fibroblasts; Histiocytes; Humans; Keratins; Psoriasis; Skin

Light microscopic examination of a basalioma (basal cell carcinoma) revealed unusual keratinizing cells resembling signet ring cells with pink cytoplasmic inclusions. Ultrastructurally the inclusions consisted of filamentous masses encircled by abundant tonofilaments giving a striking picture of abnormal individual tumor cell keratinization.

Topics: Aged; Carcinoma, Basal Cell; Cytoplasm; Humans; Keratins; Male; Skin Neoplasms

Topics: Adolescent; Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Eyelid Neoplasms; Eyelids; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Radiation Protection; Radiotherapy; Tears; Telangiectasis

Electron microscopic analyses of basaloid cell papillomas of the solid and papillomatous types are reported. The submicroscopic organization is described. Some of the ultrastructural findings, e.g. an increased number of mitochondria, a certain mitochondrial polymorphismus, the occurrence of irregularly shaped intracytoplasmic vesicles, the abundance of endoplasmic reticulum hypertrophy and the remarkable presence of microtubule-like structures, an unusual finding in a material fixed at the temperature used, are indicating an altered metabolic activity. The alternating presence and absence of keratohyalin is found to be submicromorphologically related to the formation of A- respectively B-cells. This is compared with the formation of parakeratosis in psoriatic lesions without keratohyalin. A formation of orthokeratosis as seen by the light microscopical procedure seems possible without preceeding occurrence of keratohyalin.

Topics: Carcinoma, Basal Cell; Cell Nucleus; Cytoplasm; Cytoplasmic Granules; Endoplasmic Reticulum; Humans; Hyalin; Keratins; Keratosis; Microscopy, Electron; Microtubules; Mitochondria; Parakeratosis; Ribosomes; Skin Neoplasms; Temperature

Topics: Adolescent; Carcinoma, Basal Cell; Humans; Keratins; Male; Mandibular Neoplasms; Nevus; Odontogenic Cysts

Topics: Abnormalities, Multiple; Adult; Carcinoma, Basal Cell; Chromosome Aberrations; Chromosome Disorders; Creatinine; Female; Humans; Jaw Diseases; Keratins; Male; Meningioma; Metabolic Clearance Rate; Middle Aged; Odontogenic Cysts; Phosphates; Syndrome

Topics: Carcinoma, Basal Cell; Cell Differentiation; Cells, Cultured; Contact Inhibition; DNA, Neoplasm; Humans; In Vitro Techniques; Keratins; Microscopy, Electron; Mitosis; Thymidine; Tritium

Topics: Adult; Bone Cysts; Carcinoma, Basal Cell; Diagnosis, Differential; Epidermal Cyst; Humans; Jaw Diseases; Keratins; Male; Ribs; Skin; Skin Neoplasms; Syndrome

Topics: Carcinoma, Basal Cell; Humans; Ichthyosis; Keratins; Keratosis; Microscopy, Electron; Mitochondria; Psoriasis; Skin Neoplasms

Topics: Aging; Birefringence; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemistry Techniques, Analytical; Humans; Keratins; Keratosis; Microscopy, Polarization; Skin; Skin Neoplasms; Staining and Labeling