involucrin and Hyperplasia

Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett's intestinal differentiation; however, in mice, basal progenitor cell-specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE.

Topics: Animals; Bone Morphogenetic Protein Receptors, Type I; Bone Morphogenetic Proteins; Cell Differentiation; Cells, Cultured; Eosinophilic Esophagitis; Epithelial Cells; Esophagus; Follistatin; Genes, Reporter; Humans; Hyperplasia; Mice; Mice, Inbred C57BL; Morphogenesis; NF-E2-Related Factor 2; Oxidative Stress; Protein Precursors; Reactive Oxygen Species; Signal Transduction

To address the long-known relationship between supernumerary centrosomes and cancer, we have generated a transgenic mouse that permits inducible expression of the master regulator of centriole duplication, Polo-like-kinase-4 (Plk4). Over-expression of Plk4 from this transgene advances the onset of tumour formation that occurs in the absence of the tumour suppressor p53. Plk4 over-expression also leads to hyperproliferation of cells in the pancreas and skin that is enhanced in a p53 null background. Pancreatic islets become enlarged following Plk4 over-expression as a result of equal expansion of α- and β-cells, which exhibit centrosome amplification. Mice overexpressing Plk4 develop grey hair due to a loss of differentiated melanocytes and bald patches of skin associated with a thickening of the epidermis. This reflects an increase in proliferating cells expressing keratin 5 in the basal epidermal layer and the expansion of these cells into suprabasal layers. Such cells also express keratin 6, a marker for hyperplasia. This is paralleled by a decreased expression of later differentiation markers, involucrin, filaggrin and loricrin. Proliferating cells showed an increase in centrosome number and a loss of primary cilia, events that were mirrored in primary cultures of keratinocytes established from these animals. We discuss how repeated duplication of centrioles appears to prevent the formation of basal bodies leading to loss of primary cilia, disruption of signalling and thereby aberrant differentiation of cells within the epidermis. The absence of p53 permits cells with increased centrosomes to continue dividing, thus setting up a neoplastic state of error prone mitoses, a prerequisite for cancer development.

Topics: Animals; Cell Proliferation; Cells, Cultured; Centrioles; Centrosome; Cilia; Filaggrin Proteins; Hyperplasia; Intermediate Filament Proteins; Islets of Langerhans; Membrane Proteins; Mice; Protein Precursors; Protein Serine-Threonine Kinases

The mouse cholesterol sulfotransferase St2b2 contributes to epidermal differentiation by biosynthesizing cholesterol sulfate (CS) from cholesterol in the epidermis. 12-O-Tetradecanoylphorbol-13-acetate (TPA) causes epidermal hyperplasia, an abnormal increase in epidermal cell numbers resulting from aberrant cell differentiation and an increase in St2b2 protein levels. The mechanisms underlying enhanced St2b2 expression and the pathophysiologic significance of the increased expression are unclear, however. To verify whether increased St2b2 levels are necessary for TPA-induced epidermal hyperplasia, the effects of St2b2-specific small hairpin RNA (St2b2-shRNA) on hyperplasia were examined in mice. St2b2-shRNA clearly suppressed TPA-induced epidermal hyperplasia and the expression of a marker of epidermal differentiation, involucrin (INV). Interestingly, treating mouse epidermal cells with tumor necrosis factor-alpha (TNFα) increased St2b2 expression. Furthermore, treatment with TNFα-siRNA or anti-TNF receptor antibodies reduced the TPA-induced enhancement of St2b2 expression. Treatment with BAY 11-7082, a specific inhibitor of nuclear factor-kappa B (NF-κB), diminished TPA-induced St2b2 expression. These results suggested that enhancement of St2b2 expression by TPA treatment occurs mainly through the TNFα-NF-κB inflammatory signaling pathway, which in turn leads to increased CS concentrations in epidermal cells and hyperplasia.

Topics: Animals; Antibodies; Cholesterol Esters; Epidermis; Female; Hyperplasia; Inflammation; Mice; Mice, Inbred Strains; NF-kappa B; Nitriles; Protein Precursors; Receptors, Tumor Necrosis Factor; RNA, Small Interfering; Signal Transduction; Skin Neoplasms; Sulfones; Sulfotransferases; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, regulates multiple cellular responses such as Ca(2+) signaling, growth, survival, and differentiation. Because sphingosine kinase (SphK) is the enzyme directly responsible for production of S1P, many factors have been identified that regulate its activity and subsequent S1P levels. Here we synthesized a previously unidentified SphK activator, K6PC-5, and have studied its effects on intracellular Ca(2+) signaling in HaCaT cells and epidermal differentiation in murine skin. K6PC-5, a hydrophobic compound chemically named N-(1,3-dihydroxyisopropyl)-2-hexyl-3-oxo-decanamide, activated SphK (obtained from C57BL/6 murine blood and F9-12 cell lysates) in a dose-dependent manner. K6PC-5 induced both intracellular Ca(2+) concentration ([Ca(2+)](i)) oscillations in HaCaT cells and Ca(2+) mobilization in hairless mouse epidermis. Both dimethylsphingosine (DMS) and dihydroxysphingosine (DHS), SphK inhibitors, and transfection of SphK1-siRNA blocked K6PC-5-induced increases in [Ca(2+)](i). The K6PC-5-induced [Ca(2+)](i) oscillations were dependent on thapsigargin-sensitive Ca(2+) stores and Ca(2+) entry, but independent of the classical phospholipase C-mediated pathway. In addition, K6PC-5 enhanced the expression of involucrin and filaggrin, specific differentiation-associated marker proteins in HaCaT cells, whereas transfection of SphK1-siRNA blocked the increase of involucrin. Topical K6PC-5 also enhanced the expression of involucrin, loricrin, filaggrin, and keratin 5 in intact murine epidermis. Finally, topical K6PC-5 inhibited epidermal hyperplasia by exerting antiproliferative effects on keratinocytes in murine epidermis. These results suggest that K6PC-5 acts to regulate both differentiation and proliferation of keratinocytes via [Ca(2+)](i) responses through S1P production. Thus, regulation of S1P levels may represent a novel approach for treatment of skin disorders characterized by abnormal differentiation and proliferation, such as atopic dermatitis and psoriasis.

Topics: Amides; Animals; Calcium; Calcium Signaling; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Proliferation; Enzyme Activators; Epidermis; Female; Filaggrin Proteins; Humans; Hyperplasia; Intermediate Filament Proteins; Keratin-5; Keratinocytes; Lysophospholipids; Membrane Proteins; Mice; Mice, Hairless; Mice, Inbred C57BL; Neoplasms, Germ Cell and Embryonal; Phosphotransferases (Alcohol Group Acceptor); Protein Precursors; Sphingosine; Teratocarcinoma

Overwhelming evidence has demonstrated tobacco smoke (TS) is causally associated with various types of cancers, especially lung cancer. Sustained epithelial cell hyperplasia and squamous metaplasia are considered as preneoplastic lesions during the formation of lung cancer. The cellular and molecular mechanisms leading to lung cancer due to TS are not clear. Mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1) can be activated by various stimuli and play a critical role in the control of cell proliferation and differentiation. To date, information on the response of the MAPK/AP-1 pathway during hyperplasia and squamous metaplasia induced by TS is lacking. We therefore investigated the effects of TS on the development of epithelial hyperplasia and squamous metaplasia, regulation of MAPK/AP-1 activation, and expression of AP-1-regulated cell cycle proteins and differentiation markers in the lungs of rats. Exposure of rats to TS (30 mg/m(3) or 80 mg/m(3), 6 h/day, 3 days/week for 14 weeks) dramatically induced cell proliferation and squamous metaplasia in a dose-dependent manner, effects that paralleled the activation of AP-1-DNA binding activity. Phosphorylated ERK1/2, JNK, p38 and ERK5 were significantly increased by exposure to TS, indicating the activation of these MAPK pathways. Expression of Jun and Fos proteins were differentially regulated by TS. TS upregulated the expression of AP-1-dependent cell cycle proteins including cyclin D1 and proliferating cell nuclear antigen (PCNA). Among the AP-1-dependent cell differentiation markers, keratin 5 and 14 were upregulated, while loricrin, filaggrin and involucrin were downregulated following TS exposure. These findings suggest the important role of MAPK/AP-1 pathway in TS-induced pathogenesis, thus providing new insights into the molecular mechanisms of TS-associated lung diseases including lung cancers.

Topics: Animals; Cell Proliferation; Cyclin D1; Enzyme Activation; Filaggrin Proteins; Hyperplasia; Intermediate Filament Proteins; JNK Mitogen-Activated Protein Kinases; Keratins; Lung Neoplasms; Male; Membrane Proteins; Metaplasia; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Proliferating Cell Nuclear Antigen; Protein Precursors; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Rats; Rats, Inbred WKY; Signal Transduction; Smoking; Transcription Factor AP-1

Ionic fluxes are important for critical aspects of keratinocyte differentiation, including synthesis of differentiation-specific proteins, enzymatic catalysis of protein cross-linking, post-transcriptional processing of profilaggrin, and lipid secretion. The epithelial sodium channel is expressed in epidermis and the expression of its alpha and beta subunits is enhanced as keratinocytes differentiate. In order to ascertain the role of the epithelial sodium channel in epidermal differentiation, we examined skin of mice in which the epithelial sodium channel alpha subunit had been deleted. Newborn -/- mice, in which the alpha subunit had been completely inactivated, demonstrated epithelial hyperplasia, abnormal nuclei, premature secretion of lipids, and abnormal keratohyaline granules. In addition, immunohistochemistry demonstrated that expression of the differentiation markers K1, K6, and involucrin were abnormal. These data suggest that the epithelial sodium channel modulates ionic signaling for specific aspects of epidermal differentiation, such as synthesis or processing of differentiation- specific proteins, and lipid secretion.

Topics: Animals; Biopsy; Cell Differentiation; Epidermal Cells; Epidermis; Epithelial Sodium Channels; Gene Expression; Hyperplasia; Keratinocytes; Keratins; Lipid Metabolism; Mice; Mice, Knockout; Microscopy, Electron; Protein Precursors; Sodium; Sodium Channels

Corn1 is an autosomal recessive mutation characterized by corneal epithelial hyperplasia and stromal neovascularization. The aim of the present study is to examine the expression patterns of specific epithelial and stromal proteins in corn/corn1 mutant mice.. Immunohistochemistry with antibodies directed against keratins 1, 4, 5, 12, and 14 as well as loricrin, filaggrin, and involucrin were performed in corn1/corn1 and wild type, A.By/SnJ strain, mice at 4 weeks of age. Western blot hybridization was performed to confirm the presence of involucrin in corneas. In situ and northern blot hybridization were used to evaluate the expression of keratin 12, lumican, and keratocan in these mice.. In corn1/corn1 mice, focal areas of corneal epithelial hyperplasia alternate with epithelium with normal appearance. Both regions of normal and hyperplastic corneal epithelium were labeled by anti-keratin 12 antibodies through all corneal epithelial layers. The anti-keratin 14 antibody only labeled the basal cell layer in normal epithelial areas, whereas it labeled both basal and suprabasal cell layers in hyperplastic areas. In wild type mice, anti-keratin 12 antibodies labeled all corneal epithelial layers, whereas anti-keratin 14 labeled the basal corneal epithelial cells only. Positive staining by anti-involucrin antibody was demonstrated in the basal corneal epithelial layer of wild type mice and normal areas of corn1/corn1 mice. Similarly, as observed with anti-keratin 14 antibody, the anti-involucrin antibody labeled both basal and suprabasal cell layers of hyperplastic corneal epithelium of corn1/corn1 mice. Antibodies against keratin 1, keratin 4, loricrin, and fillagrin did not label the corneas of wild type mice or corn1/corn1 mice. Northern hybridization indicated that the expressions of keratocan and lumican mRNA levels were up regulated in corn1/corn1 mice, but keratin 12 mRNA remained similar to that of the wild type mice. In situ hybridization revealed that the lumican mRNA was detected in epithelial and stromal cells of corn1/corn1 mice, whereas keratocan mRNA was only detected in stromal cells.. Hyperproliferative epithelial cells of corn1/corn1 mice have increased levels of expression of keratin 14 and involucrin, but do not exhibit the phenotypical characteristics of cornification. These observations indicate that factors associated with the phenotypes of corn1/corn1 mice do not alter the cornea-type epithelial differentiation of keratin 12 expression, but cause aberrant expression of lumican by corneal epithelial cells.

Topics: Animals; Blotting, Northern; Blotting, Western; Chondroitin Sulfate Proteoglycans; Corneal Neovascularization; Corneal Stroma; Epithelium, Corneal; Eye Proteins; Fibroblasts; Filaggrin Proteins; Gene Expression; Hyperplasia; In Situ Hybridization; Intermediate Filament Proteins; Keratan Sulfate; Keratins; Lumican; Membrane Proteins; Mice; Mice, Mutant Strains; Protein Precursors; RNA, Messenger

In prostanoid biosynthesis, the first two steps are catalyzed by cyclooxygenases (COX). In mice and humans, deregulated expression of COX-2, but not of COX-1, is characteristic of epithelial tumors, including squamous cell carcinomas of skin. To explore the function of COX-2 in epidermis, a keratin 5 promoter was used to direct COX-2 expression to the basal cells of interfollicular epidermis and the pilosebaceous appendage of transgenic mouse skin. COX-2 overexpression in the expected locations, resulting in increased prostaglandin levels in epidermis and plasma, correlated with a pronounced skin phenotype. Heterozygous transgenic mice exhibited a reduced hair follicle density. Moreover, postnatally hair follicle morphogenesis and thinning of interfollicular dorsal epidermis were delayed. Adult transgenics showed a body-site-dependent sparse coat of greasy hair, the latter caused by sebaceous gland hyperplasia and increased epicutaneous sebum levels. In tail skin, hyperplasia of scale epidermis reflecting an increased number of viable and cornified cell layers was observed. Hyperplasia was a result of a disturbed program of epidermal differentiation rather than an increased proliferation rate, as reflected by the strong suppression of keratin 10, involucrin, and loricrin expression in suprabasal cells. Further pathological signs were loss of cell polarity, mainly of basal keratinocytes, epidermal invaginations into the dermis, and formation of horn perls. Invaginating hyperplastic lobes were surrounded by CD31-positive vessels. These results demonstrate a causal relationship between transgenic COX-2 expression in basal keratinocytes and epidermal hyperplasia as well as dysplastic features at discrete body sites.

Topics: Aging; Animals; Cattle; Cell Differentiation; Cell Division; Cyclooxygenase 2; Epidermis; Hair; Hair Follicle; Heterozygote; Hyperplasia; Isoenzymes; Keratins; Membrane Proteins; Mice; Mice, Transgenic; Phenotype; Promoter Regions, Genetic; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; Sebaceous Glands; Skin

In normal epidermis, beta1 integrin expression is confined to the basal layer, whereas in hyperproliferative epidermis, integrins are also expressed in the suprabasal layers. Transgenic mice in which integrins are expressed suprabasally via the involucrin promoter have a sporadic psoriatic phenotype; however, the mechanism by which integrins contribute to the pathogenesis of psoriasis is unknown. We observed activation of mitogen-activated protein kinase (MAPK) in basal and suprabasal keratinocytes of human and transgenic mouse psoriatic lesions and healing mouse skin wounds, correlating in each case with suprabasal integrin expression. Phenotypically normal human and transgenic mouse epidermis did not contain activated MAPK. Transgene-positive keratinocytes produced more IL-1alpha than controls did, and keratinocyte MAPK could be activated by ligation of suprabasal integrins or treatment with IL-1alpha. Constitutive activation of MAPK increased the growth rate of human keratinocytes and delayed the onset of terminal differentiation, recreating many of the histological features of psoriatic epidermis. We propose that activation of MAPK by integrins, either directly or through increased IL-1alpha production, is responsible for epidermal hyperproliferation in psoriasis and wound healing, and that the sporadic phenotype of the transgenic mice may reflect the complex mechanisms by which IL-1 release and responsiveness are controlled in skin.

Topics: Animals; Antigens, Differentiation; Cell Differentiation; Cell Division; Cell Line, Transformed; Cells, Cultured; Enzyme Activation; Epidermis; Genes, Synthetic; Humans; Hyperplasia; Integrin beta1; Integrins; Interleukin-1; Keratinocytes; MAP Kinase Signaling System; Mice; Mice, Transgenic; Microscopy; Microscopy, Fluorescence; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Phenotype; Promoter Regions, Genetic; Protein Precursors; Psoriasis; Receptors, Collagen; Recombinant Fusion Proteins; Transfection; Wound Healing

The nature of clear cell acanthoma has not been clarified, although many hypotheses have been proposed, including a benign neoplasm derived from epidermis or the acrosyringium, or a non-specific dermatosis. In this study, seven cases of clear cell acanthoma were analysed by immunohistochemical techniques, using various monoclonal antikeratin antibodies, and antibodies against filaggrin, involucrin and epithelial membrane antigen. Different immunoreactivities were noted between clear cell acanthoma and a normal eccrine gland, including the acrosyringium. Immunoreactivities of clear cell acanthoma were almost identical to those of normal epidermis, although some antibodies gave a different staining pattern between clear cell acanthoma and normal epidermis. The expression of cytokeratins in psoriatic epidermis has been reported to change as a result of abnormal differentiation or maturation. Clear cell acanthoma showed a similar staining pattern to inflammatory dermatoses such as psoriasis vulgaris, lichen planus and discoid lupus erythematosus. We speculate that clear cell acanthoma is a localized form of inflammatory dermatosis rather than a neoplasm.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Epidermis; Filaggrin Proteins; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; Mucins; Protein Precursors

Involucrin is a major structural protein specific to the cross-linked cell envelope found in the stratum corneum of stratified squamous epithelium. This protein is considered to be an excellent immunohistochemical marker of normal squamous differentiation. Detection of variations to the patterns of immunostaining for involucrin may also be of value in the differential diagnosis between benign and malignant lesions. Previous studies of involucrin expression in oral mucosa have failed to clarify the effect of chronic inflammatory change upon the patterns of immunoreactivity. This study investigated involucrin staining patterns in fibrous inflammatory hyperplasia of oral mucous membrane (FIH). The results suggest that in FIH an altered pattern of involucrin immunostain occurs in areas of severe inflammatory change. This may reflect changes to the pattern of squamous differentiation in this tissue.

Topics: Dentures; Epithelium; Female; Humans; Hyperplasia; Immunoenzyme Techniques; Immunohistochemistry; Male; Mouth Mucosa; Protein Precursors; Staining and Labeling; Stomatitis, Denture

To elucidate a possible role of hematogenously transported carcinogens in pathogenesis of peripheral lung carcinoma in humans, we investigated whether the bronchiolar and alveolar epithelial cells of adult human lung xenografts in nude mice could be a target for the chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) after its systemic administration to the host mice. Peripheral lung tissues from adult humans were transplanted s.c. into nude mice, and 4NQO (15 mg/kg) was administered s.c. to the host mice at a site distant from the xenografts at 2 and 3 weeks after transplantation. The human lung xenografts were maintained for from 20 to 52 weeks, and then serial sections were examined histologically and immunohistochemically. Three types of epithelial changes, i.e. epidermoid metaplasia, papillary hyperplasia of columnar and epidermoid cells, and atypical adenomatous hyperplasia, were induced in the 4NQO group, with a statistically significant difference for these combined epithelial lesions (P less than 0.01) and for epidermoid metaplasia (P less than 0.05) compared to the control group. Some epidermoid metaplasias showed significant nuclear atypia. In addition, almost all foci of epidermoid metaplasia and papillary hyperplasia contained cells positive for carcinoembryonic antigen, suggesting both types of the lesions were preneoplastic. The morphologic characteristics of the atypical adenomatous hyperplasia were very closely similar to those of the hitherto reported preneoplastic or putative neoplastic lesions in the human peripheral lung. Our results indicated that the alveolar and bronchiolar epithelial cells of human lung xenografts were affected by systemically applied 4NQO, and subsequently underwent transformation to a preneoplastic state.

Topics: 4-Nitroquinoline-1-oxide; Aged; Animals; Bronchi; Bronchial Neoplasms; Carcinoembryonic Antigen; Female; Humans; Hyperplasia; Injections, Subcutaneous; Male; Mice; Mice, Nude; Middle Aged; Precancerous Conditions; Protein Precursors; Transplantation, Heterologous

As the distribution pattern of cytokeratin (CK), filaggrin and involucrin has recently been suggested to discriminate between benign and malignant epithelial growths, biopsies of healthy oral mucosa, leukoplakias without and with dysplasia and squamous cell carcinomas were examined immunohistochemically using a panel of 4 monoclonal antibodies (AB) against different cytokeratin polypeptides (34 beta E12, KL1 and Pkk1) and filaggrin as well as a polyclonal AB to involucrin. Major and statistically significant differences were observed in the profiles of CKs (except Pkk1), filaggrin and involucrin between leukoplakias without and with epithelial dysplasia. However, the alteration in the expression of CKs, filaggrin and involucrin proved to be not a constant feature in leukoplakias with dysplasia as a considerable portion (20-25%) of them revealed the profiles of CKs, filaggrin and involucrin similar to those of benign leukoplakias, and vice versa. Immunostaining of these antigens did not define the diagnosis of dysplasia in leukoplakias more precisely than grading in conventional histology can do so far. However, immunohistochemical sensitivity in detecting a broad range of variation in the abnormal maturation patterns of keratinocytes in leukoplakias with dysplasia can be used to divide these lesions into subgroups to elucidate their prognosis in follow-up studies.

Topics: Carcinoma, Squamous Cell; Epithelium; Female; Filaggrin Proteins; Humans; Hyperplasia; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Leukoplakia, Oral; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Phosphoproteins; Protein Precursors

Thirty-eight biopsy specimens were examined for involucrin reactivity by an immunoperoxidase technique. The sampling consisted of specimens diagnosed as normal oral mucosa, reactive epithelial hyperplasia, lichen planus (LP), nonspecific lichenoid stomatitis (NLS), lichenoid dysplasia (LD), carcinoma in situ, and squamous cell carcinoma (SCCa) on routine hematoxylin and eosin examination. Findings were consistent with prior observations of involucrin reactivity in skin and cervical-vaginal mucosa. Specifically, conditions characterized by predominance of mature squamous epithelial cells (superficial layers of normal and hyperplastic oral epithelium, NLS, and LP) exhibited strong involucrin reactivity in such areas. In contrast, atypical or dysplastic lichenoid lesions (LD), as well as carcinoma in situ, despite squamoid differentiation, demonstrated irregular distribution of involucrin, suggesting disturbances in terminal differentiation. Invasive components of SCCa revealed markedly diminished involucrin expression. These findings support prior evidence that LP and LD are biologically distinct lesions. Clinically and microscopically, both may be morphologically similar. However, involucrin reactivity should be helpful in distinguishing difficult cases. Accordingly, we suggest that the use of involucrin immunoreactivity may prove to be a valuable adjunct in the separation of similar lichenoid oral conditions.

Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Hyperplasia; Immunoenzyme Techniques; Lichen Planus; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Protein Precursors; Stomatitis