bromochloroacetic-acid and Papilloma--Intraductal

We applied immunocytochemistry to fine needle aspiration (FNA) breast lesion slides in an attempt to enhance their objectivity and specificity.. We analysed 56 FNA specimens from patients with histologically confirmed breast lesions, using 34βE12 and p63 antibodies. Immunostained slides were examined in terms of both solitary positive cells (within clusters and non-clusters) and positive clusters within a slide.. Positive scores (≥2) for p63(+) cells and percentages of p63(+) clusters differed significantly (P < 0.001) between malignant (3 of 34; 9%) and benign (11 of 22; 50%) cases and varied between benign and malignant groups: intraductal papilloma (IDP) (2 of 8), other benign lesions (9 of 14), ductal carcinoma in situ (DCIS) (1 of 11) and invasive carcinoma (IC) (2 of 23). Similarly, 34βE12 scores were higher in benign cases (IDP, 8 of 8; other benign, 9 of 14) than in malignant cases (DCIS, 1 of 11; IC, 3 of 23). As well as a significant difference between benign and malignant cases (17 of 22, 77% versus 4 of 34, 12%; P < 0.001), the percentage of 34βE12(+) clusters was significantly higher in IDP compared with DCIS (P = 0.001).. The immunostaining of FNA breast specimens for p63 and 34βE12 may help in difficult diagnoses.

Topics: Biomarkers, Tumor; Biopsy, Fine-Needle; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Cytodiagnosis; Diagnosis, Differential; Humans; Keratins; Membrane Proteins; Papilloma, Intraductal

An examination was performed on 16 intraductal proliferative breast lesions diagnosed as intraductal papillomas (IP) or usual ductal hyperplasia (UDH), which were followed up for more than 3 years. An immunohistochemical marker panel combining myoepithelial markers, high-molecular-weight keratin (HMWK) and neuroendocrine markers was used. Two of 11 IP cases were re-evaluated as atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). These cases developed breast cancer after the first operation. One IP case showed repeated recurrences. None of the other IP and UDH cases had breast cancer or recurrence. The ADH, DCIS and the recurrent IP showing a solid growth lacked myoepithelia, but the recurrent IP expressed HMWK, immunohistochemically. Interestingly, these three lesions were weakly positive for neuroendocrine markers. All other IPs and UDHs, including lesions having solid components, were negative for neuroendocrine markers, and most of them were positive for myoepithelial markers and/or HMWK. A combination of the above immunohistochemical markers seems useful to evaluate intraductal proliferative lesions and to predict their prognosis. In particular, intraductal proliferative lesions with solid components exhibiting positivity for neuroendocrine markers should be followed up carefully to monitor breast cancer risk or recurrence.

Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Breast Neoplasms, Male; Carcinoma, Intraductal, Noninfiltrating; Chromogranin A; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Male; Membrane Proteins; Microfilament Proteins; Middle Aged; Neoplasm Recurrence, Local; Papilloma, Intraductal; Prognosis; Smooth Muscle Myosins

Papillary breast lesions remain a source of diagnostic confusion because the full range of epithelial proliferations may arise within, or secondarily involve, papilloma. The expression of p63 and high-molecular-weight cytokeratins (HMWCK) was studied simultaneously in 33 papillary lesions including intraductal papilloma (IP, n = 10), atypical papilloma (AP, n = 8) and intraductal papillary carcinoma (IPC, n = 15) by double immunostaining. The myoepithelial cell nuclei were stained dark brown whereas the cytoplasms of usual ductal hyperplasia (UDH) and myoepithelium were stained purple. The myoepithelial layer was recognized as a dark brown dotted line at the epithelial stromal junction in all IP (10/10), most AP (7/8) and some IPC (7/15), suggesting that the retained myoepithelial layer in the papillary processes does not necessarily guarantee benignity. However, the malignant epithelial cells in AP and IPC were typically recognized as monotonous populations unstained with either chromogen. These monotonous cells contrasted with the proliferating cells of UDH in papilloma, which had intense purple cytoplasm in a mosaic-like fashion. The present data suggest that the double immunostaining with the two popular antibodies p63 and HMWCK is a useful tool for reproducible classification of papillary breast lesions.

Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; DNA-Binding Proteins; Female; Fluorescent Antibody Technique, Direct; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Mammary Glands, Human; Middle Aged; Molecular Weight; Papilloma, Intraductal; Retrospective Studies; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

We examined myoepithelial status in intraductal papillary carcinoma (IPC) along with the expression of high-molecular weight cytokeratin (HMWK) and neuroendocrine markers, with special reference to the differential diagnosis of solid intraductal papillary carcinoma(SIPC) and intraductal papilloma with usual ductal hyperplasia (IP-UDH). Twenty-six (93%) of the twenty-eight intraductal papillomas (IP) had myoepithelial cells in >70% of the epithelial-stromal interface of the intraluminal proliferating component. Six (29%) of twenty-one SIPC had almost complete myoepithelial layer like IP-UDH at the epithelial-stromal interface. HMWK (34 beta E-12) was diffusely positive in 14 (93%) of 15 IP-UDH, but 16 (76%) of 21 SIPC were completely negative for HMWK. Neuroendocrine markers were positive in 14 (67%) of SIPC, but all 28 IPs were completely negative. If only the presence of myoepithelial cells is emphasized as a benign hallmark, about 30% of SIPCs may be underdiagnosed as IP-UDH. However, by using a combination of myoepithelial markers, HMWK, and neuroendocrine markers, all of the 36 solid intraductal papillary lesions were properly classified as benign and malignant. Solid intraductal papillary lesions meeting at least two of the following criteria are highly likely to be malignant: (1) absence of myoepithelial cells(<10% of epithelial-stromal interface of intraluminal proliferating component), (2) negative HMWK(<10%), (3) positive neuroendocrine markers (>10%).

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Mammary Glands, Human; Middle Aged; Molecular Weight; Nerve Tissue Proteins; Papilloma, Intraductal

We studied 50 papillary lesions (25 papillomas and 25 papillary ductal carcinomas in situ, DCIS) diagnosed at Singapore General Hospital, for immunohistochemical expression of cytokeratin (CK) 5/6, CK14, and 34betaE12. The immunoscore (proportion of stained cells multiplied by staining intensity) was compared between the two groups. Cytokeratin expression was corroborated by confocal microscopy. Results were applied to a separate series of 43 papillary tumors from Hong Kong (HK). CK5/CK6, CK14, and 34betaE12 showed higher immunoscores in papillomas (mean values, 107.6, 186.6, and 113.1, respectively) than papillary DCIS (mean values, 12, 29.6, and 34.5, respectively; P<0.0001, P<0.001, and P<0.02, respectively). A cutoff immunoscore threshold of 50 appeared discriminatory between papilloma and papillary DCIS, and this value was applied to the HK cases, with CK5/CK6, CK14, and 34betaE12 correctly predicting 25 (89.3%), 26 (92.9%), and 27 (96.4%), respectively, of 28 HK lesions labeled as papillomas; while they corroborated 13 (86.7%), 13 (86.7%), and 5 (33.3%), respectively, of 15 HK cases diagnosed as papillary DCIS. Review of discordant cases showed that lesions were small, derived from core biopsies, or disclosed accompanying invasive carcinoma. When both SGH and HK cases were combined as a group, the sensitivity of an immunoscore of 50 or less in the diagnosis of papillary DCIS was 95%, 85%, and 62.5% for CK5/CK6, CK14, and 34betaE12, respectively, while the specificity was 86.8%, 94.3%, and 86.8%, respectively. CK immunohistochemistry can aid in evaluating papillary breast lesions. 34betaE12 does not appear as useful in identifying papillary DCIS.

Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Mammary Glands, Human; Middle Aged; Papilloma, Intraductal; Predictive Value of Tests

We report here the first case of sebaceous gland metaplasia arising within an intraductal papilloma of the breast of a 70-year-old female. Several lobules and nests composed of clear cells closely resembling sebaceous glands of the skin were discovered within an intraductal papilloma of the breast. Squamous metaplasia was also noted in certain areas of the tumor. Immunohistochemically, the cells of the lobules and nests stained positively for monoclonal antibodies anti-cytokeratin 14 and epithelial membrane antigen. This study confirms a novel type of metaplasia of the breast.

Topics: Aged; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Breast Neoplasms; Carrier Proteins; Female; Glycoproteins; Humans; Immunohistochemistry; Keratins; Membrane Transport Proteins; Metaplasia; Mucin-1; Papilloma, Intraductal; Sebaceous Glands

According to current concepts, benign proliferative breast disease (BPBD) is a direct precursor of breast cancer, in a spectrum ranging from ductal hyperplasia to overtly invasive carcinoma. In this study, comparative genomic hybridization (CGH) was used to screen ductal hyperplasia and other BPBD lesions and ductal carcinoma in situ (DCIS) for common genomic abnormalities, to test the relationship between these hyperplastic and neoplastic lesions. Immunohistochemistry for cytokeratin 5/6 was used as a diagnostic adjunct to distinguish ductal hyperplasia from DCIS. A total of 42 cases of BPBD comprising ductal hyperplasia of the usual type (n=14), papilloma (n=22), tubular adenoma (n=3), and adenosis (n=3), as well as 52 cases of DCIS, were studied. All cases of BPBD consistently displayed the presence of a subpopulation of cytokeratin 5/6-expressing basal-type cells within the proliferative lesion, whereas all of the non-high-grade and most of the high-grade DCIS lesions lacked cytokeratin 5/6-positive cells. Whereas gross genomic alterations, as determined by CGH, were undetectable in BPBD, distinct genetic changes characterized all cases of DCIS, with one exception. These results confirm the usefulness of cytokeratin 5/6 immunohistology in the diagnosis of BPBD and neoplastic breast lesions and support the view that BPBD and DCIS are not closely related entities and that BPBD is not an obligate direct precursor of DCIS.

Topics: Adenoma; Breast Diseases; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Chromosome Aberrations; Female; Fibrocystic Breast Disease; Humans; Hyperplasia; In Situ Hybridization, Fluorescence; Keratins; Molecular Weight; Nucleic Acid Hybridization; Papilloma, Intraductal; Precancerous Conditions

Benign proliferative nipple duct lesions (PNDLs) pose a diagnostic problem for clinicians and pathologists. Clinically, they may be associated with skin changes typically present in Paget's disease of the nipple. The identification of numerous scattered cells in the epidermis that are immunoreactive for low-molecular-weight cytokeratin may lead to further confusion with Paget's disease. We studied the nipple epidermis in nine cases of PNDL and compared them with 26 histologically normal nipples from mastectomy specimens. CAM 5.2 and anticytokeratin 7 (CK7) immunoreactive cells were identified in the epidermis of seven of nine nipples associated with PNDL. The cytokeratin-positive cells appeared cytologically benign and were dispersed singly (scattered in seven of seven cases and frequent in four of seven cases) or formed small aggregates with occasional tubular structures (three of seven cases) in the basal and middle layers of the epidermis. In two of seven cases, these epidermal immunoreactive cells showed continuity with the underlying PNDL, suggesting the spread or continuation of lesional cells to the epidermis. Dispersed single immunoreactive cells were identified in small numbers (scattered) in the basal layer of the epidermis in 12 of 26 normal nipples and more frequently in 1 of 12 cases. In all cases, the intraepidermal cells were negative for carcinoembryonic antigen (CEA) and Her-2/neu. We conclude that intraepidermal CAM 5.2 and anti-CK7 immunoreactive cells, which are normally present in the nipple epidermis, may proliferate and form aggregates when there is an underlying PNDL. The presence of these cells does not imply Paget's disease when the intraepidermal cells have a bland cytologic appearance, fail to overexpress Her-2/neu, and there is no carcinoma within the PNDL or elsewhere in the breast.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Breast Diseases; Breast Neoplasms; Cell Division; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Middle Aged; Nipples; Papilloma, Intraductal; Skin

Topics: Aged; Aged, 80 and over; Breast Neoplasms; Carcinosarcoma; Cell Transformation, Neoplastic; Female; Humans; Keratins; Papilloma, Intraductal; S100 Proteins

Two monoclonal antibodies (MAbs) were established in 20 clones of MAbs generated against cytokeratin fraction extracted from canine squamous cell carcinoma to investigate the expression of intermediate filament proteins during tumorigenesis. These MAbs were confirmed to react with purified cytokeratin by ELISA. One monoclonal antibody, MAb32 reacted all layers of epidermis except the cornified layer and mammary myoepithelial cells but not any epithelial cells. Another antibody named MAb24 exclusively reacted the basal monolayer of epidermis, the stratum germinativum. Any positive reactions with MAb24 were not detected in normal mammary gland. From the analysis by two-dimensional gel electrophoresis followed by immunoblotting, it was revealed that MAb24-recognizing cytokeratin subunit gave a molecular weight of 57 kilodalton and a isoelectric-pH value of pI5.1, indicating type I (acidic) cytokeratin. In intraductal papillomas developed in canine mammary glands, most tumor cells were positively stained with MAb32 in addition of myoepithelial cells while no positive reaction with MAb24 was seen. In ductal carcinomas, MAb24-positive cytokeratin was begun to express by tumor cells with positive reaction of MAb32 where these cells showed infiltrative growth into the stroma. We therefore proposed that 57 kilodalton-type I cytokeratin was a molecular marker for malignant transformation in canine mammary tumor and these antibodies could be useful tools to investigate the change of cytokeratin expression during tumorigenesis.

Topics: Adenofibroma; Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Ductal, Breast; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Dog Diseases; Dogs; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Epithelium; Female; Immunoblotting; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Animal; Papilloma, Intraductal

Duct ectasias (n = 2) and different types of benign canine mammary tumours (n = 19) were studied immunohistochemically with monoclonal antibodies (MoAbs) directed against various human keratin types (K), alpha-smooth muscle actin, vimentin, and desmin. In the duct ectasias and in most tumours the epithelial structures revealed an inner and outer cell layer. The inner cell layer was characterized by labelling with K 7, 8, 18, 19 and mostly also with K 4 and/or K 10 MoAbs. The outer cell layer was almost invariably labelled by K 14, K 14 and 17, and a-smooth muscle actin MoAbs. The labelling patterns of both duct ectasias and tumours corresponded largely to the patterns observed in normal mammary gland tissue, although a more distinct heterogeneity was seen. Tumours histomorphologically assumed to be of a myoepithelial origin did not show immunohistochemical features of myoepithelial cells. The myoepithelial nature of the vast majority of spindle-shaped cells present in the adenomas of the complex type and in the fibroadenomas of the benign mixed type could not be confirmed immunohistochemically. These cells, however, unequivocally expressed vimentin, suggesting proliferation of stromal cells in these tumours, which in the fibroadenomas of the benign mixed type may show metaplasia to bone or cartilage. In the duct ectasias and in some tumours, a fraction of elongated stromal cells, probably representing myofibroblasts, was labelled with the alpha-smooth muscle actin MoAb.

Topics: Actins; Adenoma; Animals; Antibodies, Monoclonal; Desmin; Dilatation, Pathologic; Dog Diseases; Dogs; Female; Fibroadenoma; Immunoenzyme Techniques; Immunophenotyping; Intermediate Filament Proteins; Keratins; Male; Mammary Glands, Animal; Mammary Neoplasms, Animal; Mastitis; Papilloma, Intraductal; Vimentin