All Benign and Malignant Apocrine Breast Lesions Over-Express Claudin 1 and 3 and Are Negative for Claudin 4.

Invasive apocrine carcinoma of the breast is an uncommon triple negative tumour that lacks a specific therapeutic target. Apocrine metaplasia of the breast shares common morphological features with apocrine carcinoma, and was previously found to consistently over-express claudin 1 and to lack claudin 4. This study was aimed at finding whether apocrine carcinoma, and other related apocrine breast lesions, have similar claudin profile. The immunohistochemical expression of claudin 1, 3 and 4 was studied in 11 cases of in situ and invasive apocrine breast carcinoma, 7 benign apocrine lesions and 45 consecutive morphologically non-apocrine triple negative breast carcinomas. All cases were also immunostained for Gross Cystic Disease Fluid Protein-15 (GCDFP-15), a marker for apocrine differentiation. Apocrine breast lesions maintained their expression pattern from benign through DCIS to invasive carcinoma; all showing strong expression of claudin 1 and 3 and absence of claudin 4. The same pattern of expression was seen in 2 out of the 45 morphologically non-apocrine tumours, but both showed strong positive staining for GCDFP-15. It is concluded that all benign and malignant apocrine lesions of the breast have a consistent pattern of claudin 1, 3 and 4 expression, suggesting the presence of a specific pathway for the development of invasive apocrine carcinoma. The over-expression of claudin 1 and 3 may have therapeutic implications as targets for managing apocrine cancers.

Regulation of blood-testis barrier assembly in vivo by germ cells.

The assembly of the blood-testis barrier (BTB) during postnatal development is crucial to support meiosis. However, the role of germ cells in BTB assembly remains unclear. Herein, KitW/KitWV mice were used as a study model. These mice were infertile, failing to establish a functional BTB to support meiosis due to c-Kit mutation. Transplantation of undifferentiated spermatogonia derived from normal mice into the testis of KitW/KitWV mice triggered functional BTB assembly, displaying cyclic remodeling during the epithelial cycle. Also, transplanted germ cells were capable of inducing Leydig cell testosterone production, which could enhance the expression of integral membrane protein claudin 3 in Sertoli cells. Early spermatocytes were shown to play a vital role in directing BTB assembly by expressing claudin 3, which likely created a transient adhesion structure to mediate BTB and cytoskeleton assembly in adjacent Sertoli cells. In summary, the positive modulation of germ cells on somatic cell function provides useful information regarding somatic-germ cell interactions.-Li, X.-Y., Zhang, Y., Wang, X.-X., Jin, C., Wang, Y.-Q., Sun, T.-C., Li, J., Tang, J.-X., Batool, A., Deng, S.-L., Chen, S.-R., Cheng, C. Y., Liu, Y.-X. Regulation of blood-testis barrier assembly in vivo by germ cells.

[The expression of claudins in colonic neoplasms]. / Osobennosti ekspressii klaudinov v novoobrazovaniyakh tolstoi kishki.

AIM: the evaluation of localization claudin-1, -3 and -4 types of cancer and colon polyps. MATERIAL AND METHODS: The study included 32 colon adenocarcinoma and 86 polyps. Antibody claudin-1; -3 and -4 were used as immunohistochemical markers in this study. RESULTS: 84/118, 64/118, 52/118 reaction with claudin-1, claudin-3 and claudin-4 in cancer and colon polyps had a membrane localization, respectively. In 33 (27.9%) cases was found paradoxical reaction claudin-1; in 50 (42.4%) - a paradoxical reaction claudin-3 in 66 (55.9%) - a paradoxical reaction claudin-4. Among the paradoxical claudin reaction nuclear localization of marker was observed relatively rarely: claudin-3 in 2.5% cases of colon cancer; claudin-4 in 8.5% of colon polyps. CONCLUSION: Mislocalization claudin-3 to nucleus in colon cancer and mislocalization claudin-4 to nucleus in adenomas of the colon were detected for the first time. The potential reasons for the paradoxical expression are discussed and a review of the literature, related all the alleged mechanisms of this mislocalization is provided.

Glycoproteins in Claudin-Low Breast Cancer Cell Lines Have a Unique Expression Profile.

Claudin proteins are components of epithelial tight junctions; a subtype of breast cancer has been defined by the reduced expression of mRNA for claudins and other genes. Here, we characterize the expression of glycoproteins in breast cell lines for the claudin-low subtype using liquid chromatography/tandem mass spectrometry. Unsupervised clustering techniques reveal a group of claudin-low cell lines that is distinct from nonmalignant, basal, and luminal lines. The claudin-low cell lines express F11R, EPCAM, and other proteins at very low levels, whereas CD44 is expressed at a high level. Comparison of mRNA expression to glycoprotein expression shows modest correlation; the best agreement occurs when the mRNA expression level is lowest and little or no protein is detected. These findings from cell lines are compared to those for tumor samples by the Clinical Proteomic Tumor Analysis Consortium (CPTAC). The CPTAC samples contain a group low in CLDN3. The samples low in CLDN3 proteins share many differentially expressed glycoproteins with the claudin-low cell lines. In contrast to the situation for cell lines or patient samples classified as claudin-low by RNA expression, however, most of the tumor samples low in CLDN3 protein express the estrogen receptor or HER2. These tumor samples express CD44 protein at low rather than high levels. There is no correlation between CLDN3 gene expression and protein expression in these CPTAC samples; hence, the claudin-low subtype defined by gene expression is not the same group of tumors as that defined by low expression of CLDN3 protein.

Claudin-3 expression increases the malignant potential of lung adenocarcinoma cells: role of epidermal growth factor receptor activation.

Claudins are essential for the formation and maintenance of tight junctions (TJ). The altered expression of claudin proteins has been described in a variety of malignancies. However, the alteration of these proteins in lung adenocarcinoma (ADC) are poorly understood. Therefore, we report, based on the protein expression analysis of a total of 275 patient samples, that claudin-3 (CLDN3) expression is significantly increased in ADC tissues and is associated with cancer progression, correlating significantly with the poor survival of ADC patients (p=0.041&0.029). More importantly, forcing CLDN3 expression in ADC cells without endogenous CLDN3 expression resulted in significant increases in the cell proliferation, anchorage-dependent growth, migration and drug-resistance. In addition, epidermal growth factor (EGF) signaling pathway modulates the expression of claudins in a number of solid tumors. However, the mechanism of tight junction regulation by EGF in ADC remains unclear. To investigate this mechanisms, ADC cell lines were treated with EGF and its inhibitor. EGF unregulated CLDN3 expression via the MEK/ERK or PI3K/Akt signaling pathways and was required for the maintenance of baseline CLDN3 expression. Furthermore, downregulation of CLDN3 expression in ADC cell was found to prevent the EGF-induced increase in cell proliferation. In conclusion, our results demonstrate a novel role of CLDN3 overexpression in promoting the malignant potential of lung adenocarcinoma. This function is potentially regulated by the EGF-activated MEK/ERK and PI3K-Akt pathways.

Claudin-3 and claudin-19 partially restore native phenotype to ARPE-19 cells via effects on tight junctions and gene expression.

Mutations of claudin-19 cause severe ocular deficits that are not easily reconciled with its role in regulating the outer blood retinal barrier. ARPE-19 is a widely used culture model of the retinal pigment epithelium (RPE). ARPE-19 is unique among epithelial cell lines, because it expresses all tight junction proteins except claudin family members. ARPE-19 also loses aspects of the RPE phenotype with cell passage. This study asks whether exogenous expression of the main RPE claudins, claudin-3 and claudin-19, would restore RPE phenotype, and whether these claudins have distinct roles in RPE. An Ussing chamber was used to measure the transepithelial electrical resistance and transepithelial electrical potential. These measurements were used to estimate the permeability co-efficients of ions. The transepithelial diffusion of polyethylene glycols were used to examine the leak pathway of tight junctions. Wound-healing, quantitative RT-PCR and immunoblotting examined diverse aspects of the RPE phenotype. Over-expression of either claudin decreased the permeability of small ions and polyethylene glycol. Both claudins were slightly cation-specific, but claudin-3 was less permeable to large solutes. Claudin expression widely affected gene expression to partially restore RPE phenotype. Claudins redistributed filamentous actin from stress fibers to circumferential bands associated with tight junctions, and made wound-healing more epithelial-like. Both claudins increased the expression of genes related to RPE core functions and increased steady-state levels of phosphorylated-AKT. In conclusion, claudin-3 and claudin-19 formed general permeability barriers and affected cell morphology, proliferation, migration, AKT signaling, and gene expression. When claudins are exogenously expressed, ARPE-19 more closely model native RPE.

Prolactin and glucocorticoid signaling induces lactation-specific tight junctions concurrent with ß-casein expression in mammary epithelial cells.

Alveolar mammary epithelial cells (MECs) in mammary glands are highly specialized cells that produce milk for suckling infants. Alveolar MECs also form less permeable tight junctions (TJs) to prevent the leakage of milk components after parturition. In the formation process of less permeable TJs, MECs show a selective downregulation of Cldn4 and a localization change of Cldn3. To investigate what induces less permeable TJs through these compositional changes in Cldns, we focused on two lactogenesis-related hormones: prolactin (Prl) and glucocorticoids. Prl caused a downregulation of Cldn3 and Cldn4 with the formation of leaky TJs in MECs in vitro. Prl-treated MECs also showed low ß-casein expression with the activation of STAT5 signaling. By contrast, dexamethasone (Dex), a glucocorticoid analogue, upregulated Cldn3 and Cldn4, concurrent with the formation of less permeable TJs and the activation of glucocorticoid signaling without the expression of ß-casein. Cotreatment with Prl and Dex induced the selective downregulation of Cldn4 and the concentration of Cldn3 in the region of TJs concurrent with less permeable TJ formation and high ß-casein expression. The inhibition of Prl secretion by bromocriptine in lactating mice induced the upregulation of Cldn3 and Cldn4 concurrent with the downregulation of milk production. These results indicate that the coactivation of Prl and glucocorticoid signaling induces lactation-specific less permeable TJs concurrent with lactogenesis.

Claudin-1, -3, -4 and -7 gene expression analyses in canine prostate carcinoma and mammary tissue derived cell lines.

Claudins (CLDNs) are transmembrane proteins localised in the cell membrane of epithelial cells composing a structural and functional component of the tight junction protein complexes. In canine tumors deregulations of the CLDN expression patterns were described immunohistochemically. Targeting of claudin proteins has further been evaluated to establish novel therapeutic approaches by directed claudin binding. Precondition for the development of claudin targeting approaches in canine cells is the possibility to characterise claudin expression specifically and the availability of claudin positive cell lines. Herein PCR/qPCR assays were established allowing a rapid qualitative and quantitative characterisation of CLDN-1, -3, -4 and -7 gene expression in canine cell lines and tissues. Further commercially available antibodies were used to verify CLDN gene expression on protein level by Western blots. The developed assays were used to analyse six canine cell lines derived from mammary and prostate tissue for their CLDN-1, -3, -4 and -7 expressions. The canine cell line DT08/40 (prostate transitional cell carcinoma) was used for the establishment of specific CLDNs -1, -3, -4 and -7PCR/qPCR. The designed assays were verified by amplicon cloning and sequencing. Gene expressions were verified on protein level by Western blot. Additionally further cell lines were analysed for their CLDN-1, -3, -4 and -7 expression on mRNA and protein level (mammary derived cell lines: MTH53A (non-neoplastic), ZMTH3 (adenoma), MTH52C (carcinoma); prostate derived cell lines: DT08/46 and CT1258 (both adenocarcinoma).The screened cell lines showed expression for the CLDNs as follows: DT08/46 and DT08/40: CLDN-1, -3, -4 and -7 positive; CT1258: CLDN-1, -3, -4 and -7 negative; ZMTH3 and MTH52C: CLDN-1 and -7 positive, CLDN-3 and -4 negative; MTH53A: CLDN-1, -3 and -4 negative, CLDN-7 positive. Western blot analyses reflect the detected CLDN-1, -3, -4 and -7 expressions in the analysed cell lines. The established CLDN-1, -3, -4 and -7 PCR/qPCR assays allow a qualitative and quantitative characterisation of canine CLDN gene expression. Characterisation of CLDN expression in six canine cell lines led to the identification of two canine prostate tissue derived CLDN expressing cell lines. These cell lines serve as candidates for further research on CLDN-based functional and therapeutic approaches.

Endothelial ß-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

BACKGROUND: The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. METHODS AND RESULTS: Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial ß-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial ß-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear ß-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. CONCLUSIONS: These results demonstrate the prerequisite role of endothelial ß-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective ß-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation.

Androgen Receptor Coactivator ARID4B Is Required for the Function of Sertoli Cells in Spermatogenesis.

Defects in spermatogenesis, a process that produces spermatozoa inside seminiferous tubules of the testis, result in male infertility. Spermatogenic progression is highly dependent on a microenvironment provided by Sertoli cells, the only somatic cells and epithelium of seminiferous tubules. However, genes that regulate such an important activity of Sertoli cells are poorly understood. Here, we found that AT-rich interactive domain 4B (ARID4B), is essential for the function of Sertoli cells to regulate spermatogenesis. Specifically, we generated Sertoli cell-specific Arid4b knockout (Arid4bSCKO) mice, and showed that the Arid4bSCKO male mice were completely infertile with impaired testis development and significantly reduced testis size. Importantly, severe structural defects accompanied by loss of germ cells and Sertoli cell-only phenotype were found in many seminiferous tubules of the Arid4bSCKO testes. In addition, maturation of Sertoli cells was significantly delayed in the Arid4bSCKO mice, associated with delayed onset of spermatogenesis. Spermatogenic progression was also defective, showing an arrest at the round spermatid stage in the Arid4bSCKO testes. Interestingly, we showed that ARID4B functions as a "coactivator" of androgen receptor and is required for optimal transcriptional activation of reproductive homeobox 5, an androgen receptor target gene specifically expressed in Sertoli cells and critical for spermatogenesis. Together, our study identified ARID4B to be a key regulator of Sertoli cell function important for male germ cell development.

Identification and dynamic regulation of tight junction protein expression in human neural stem cells.

Recent reports indicate that neural stem cells (NSCs) exist in a cluster-like formation in close proximity to cerebral microvessels. Similar appearing clusters can be seen ex vivo in NSC cultures termed neurospheres. It is known that this neurosphere configuration is important for preserving stemness and a proliferative state. How NSCs form neurospheres or neuroclusters remains largely undetermined. In this study, we show that primary human NSCs express the tight junction proteins (TJPs): zonula occludens-1 (ZO-1), occludin, claudin-1, -3, -5, and -12. The relative mRNA expression was measured by quantitative polymerase chain reaction, and protein expression was confirmed by flow cytometry and immunofluorescence microscopy. Our results show that downregulation of TJPs occurs as neuronal differentiation is induced, suggesting that control of TJPs may be tied to the neuronal differentiation program. Importantly, upon specific knockdown of the accessory TJP, ZO-1, undifferentiated NSCs showed decreased levels of key stem cell markers. Taken together, our results indicate that TJPs possibly aid in maintaining the intercellular configuration of NSCs and that reduction in TJP expression consequently affects the stemness status.

Decreased expression of claudin-3 is associated with a poor prognosis and EMT in completely resected squamous cell lung carcinoma.

The deregulation of claudin-3 has been reported to correlate with the invasion and metastasis of various cancers, but little is known about its expression level and the prognostic value in squamous cell lung carcinoma (SqCC). The purpose of this study is to determine the expression levels and the prognostic value of claudin-3 in completely resected SqCC tissues, and the potential underlying mechanism. The protein expression of claudin-3, E-cadherin, ß-catenin, and vimentin in the tumor tissues from 103 patients with surgically resected SqCC was examined using immunohistochemistry, western blots, as well as semi-quantitative estimation. The claudin-3 protein level was significantly associated with E-cadherin, ß-catenin, and vimentin protein expression. A decreased claudin-3 protein level was significantly correlated with TNM stage, lymph node metastasis, and disease recurrence. Similarly, downregulation of E-cadherin was significantly correlated with lymph node metastasis and disease recurrence. Decreased ß-catenin expression also had a significant correlation with disease recurrence. Univariate analyses indicated that the T stage, lymph node metastasis, the TNM stage, and the expression of claudin-3, ß-catenin, and vimentin were significant predictors for overall survival (OS). Moreover, multivariate analyses demonstrated that the TNM stage and protein levels of claudin-3, ß-catenin, and vimentin were independent predictors for OS of SqCC patients. Claudin-3 plays an important role in the epithelial-mesenchymal transition of SqCC and might be used as a potential prognostic factor for SqCC.

The expression patterns of tight junction protein claudin-1, -3, and -4 in human gastric neoplasms and adjacent non-neoplastic tissues.

Recently, there is growing evidence that tight junction proteins are often abnormally regulated in human tumors. The function of tight junction proteins in the maintenance of normal epithelial physiology has been well discussed, but their role in the tumorigenesis of gastric cancer is less well defined. To explore the expression distinction of the tight junction proteins claudin-1, -3, and -4 expression in the gastric cancer, the expression of claudin-1, -3, and -4 in 92 gastric cancer tissues and the non-neoplastic tissues adjacent to the tumors were examined by immunohistochemistry. Compared with adjacent non-neoplastic tissues, the expression of claudin-1 was down regulated. However, the expression of claudin-3 and claudin-4 were up-regulated in gastric cancer tissue. In addition, the expression of claudin-3 is correlated with claudin-4 expression in gastric cancer. Our present study reveals that claudin-1, -3, and -4 protein expression altered between human gastric cancers and adjacent non-neoplastic tissues.

Metaplastic carcinoma show different expression pattern of YAP compared to triple-negative breast cancer.

The purpose of this study is to examine the expression of Yes-associated protein (YAP) in metaplastic carcinoma and compare to those of triple-negative breast carcinoma (TNBC) for investigation of its implication. Tissue microarrays containing 34 cases of metaplastic carcinoma and 175 cases of TNBC were constructed and immunohistochemical staining was used to evaluate expression of the following proteins: YAP and phosphorylated YAP (pYAP). According to immunohistochemical staining results of cytokeratin 5/6, EGFR, claudin 3, claudin 4, claudin 7, E-cadherin, STAT-1, androgen receptor, and GGT-1, metaplastic carcinoma and TNBC were sub-classified into six subtypes: basal-like type, molecular apocrine type, claudin-low type, immune-related type, mixed type, and null type. Comparing the expression of YAP and pYAP in metaplastic carcinoma and TNBC, the expression of nuclear YAP (p = 0.025), cytoplasmic pYAP (p = 0.010), and nuclear pYAP (p = 0.014) in tumor cell was higher in metaplastic carcinoma than TNBC. In metaplastic carcinoma, the nuclear YAP expression in tumor cell was associated with loss of E-cadherin (p = 0.020) and claudin type (p = 0.020), and the stromal YAP expression was associated with claudin 7 positivity (p = 0.003). In conclusion, the YAP expression in metaplastic carcinoma is higher than that in TNBC, representing the association of stemness and epithelial-mesenchymal transition features in metaplastic carcinoma.

[Solid pseudopapillary tumors of the pancreas: clinical and morphological characteristics, specific features of their immunophenotype, and diagnostic problems].

OBJECTIVE: To analyze 60 cases of solid pseudopapillary tumors (SPTs) of the pancreas, to reveal their most characteristic clinical and morphological features, and to study their possible histogenesis. MATERIAL AND METHODS: Sixty cases of SPTs of the pancreas underwent clinical, morphological, and immunohistochemical (IHC) examinations; a comparison group consisted of 86 pancreatic tumors of other histogenesis. RESULTS: It has been shown for the first time that SPTs are characterized by the nuclear expression of claudin 3 and the cytoplasmic expression of claudin 7. It has been also ascertained that the aberrant perinuclear (dot-like) expression of CD99 is a unique feature of these tumors. CONCLUSION: SPTs of the pancreas are distinguished by a diversity of clinical manifestations and morphological features, but have a unique immunophenotype, which can differentiate them from other types of pancreatic tumors.

Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance.

Medullary thymic epithelial cells (mTECs) are crucial for central T cell self-tolerance. Although progenitors of mTECs have been demonstrated in thymic organogenesis, the mechanism for postnatal mTEC maintenance remains elusive. We demonstrate that implantation of embryonic TECs expressing claudin-3 and claudin-4 (Cld3,4) in a medulla-defective thymic microenvironment restores medulla formation and suppresses multiorgan autoimmunity throughout life. A minor SSEA-1(+) fraction within the embryonic Cld3,4(hi) TECs contained self-renewable clonogenic TECs, capable of preferentially generating mature mTECs in vivo. Adult SSEA-1(+)Cld3,4(hi) TECs retained mTEC reconstitution potential, although the activity decreased. The clonogenicity of TECs also declined rapidly after birth in wild-type mice, whereas it persisted in Rag2(?/?) adult mice with defective thymopoiesis. The results suggest that unipotent mTEC-restricted stem cells that develop in the embryo have the capacity to functionally reconstitute the thymic medulla long-term, thus ensuring lifelong central T cell self-tolerance.

Mice stage-specific claudin 3 expression regulates progression of meiosis in early stage spermatocytes.

Claudin 3 is a protein component of the tight junction strands. Tight junctions between adjacent Sertoli cells form the blood-testis barrier (BTB). During spermatogenesis, seminiferous stage-specific expression of claudin 3 is believed to regulate the migration of preleptotene/leptotene spermatocytes across the BTB. Here, we determined the cell types expressing claudin 3 in adult mouse testis and investigated spermatogenesis after testis-specific in vivo knockdown of claudin 3. The results of in situ hybridization revealed that claudin 3 mRNA was predominantly expressed in germ cells near the basal lamina of seminiferous tubules at stages VI-IX. Furthermore, claudin 3 protein was localized not only to the BTB but also to the cell membrane of STRA8-expressing preleptotene/leptotene spermatocytes in the testis of adult ICR.Cg-Tg(Stra8-EGFP)1Ysa/YsaRbrc mice. Although claudin 3 knockdown did not affect BTB integrity, it did cause a partial delay in spermatocyte migration across the BTB. Moreover, claudin 3 knockdown resulted in a prolonged preleptotene phase during spermatogenesis. These data indicate that the seminiferous stage-specific expression and localization of claudin 3 during spermatogenesis regulate the progression of meiosis by promoting germ cell migration across the BTB.

CLDN3 expression and significance - breast carcinoma versus ovarian carcinoma.

Claudins (CLDNs) are transmembrane proteins, as normal constituents of the architecture of tight junctions. Recent studies support their involvement in carcinogenesis, as changes in CLDNs structure result in alterations in tight junctions' structure and function, facilitating malignant transformation. We aimed CLDN3 investigation in both breast and ovarian carcinoma, targeting the identification of its expression differences. The immunohistochemical assessment was performed on 20 cases of breast carcinomas (Group 1) and 19 cases of epithelial ovarian carcinomas (Group 2). Firstly, the specific panel for the molecular classification was applied for specimens of the first group. Then, all the specimens were immunostained for CLDN3 and a semi-quantitative evaluation was made, based on the percentage of positive cells and the intensity of staining. In Group 1, in the ER positive category, CLDN3 was overexpressed in five cases (four cases of luminal A and one case of luminal B subtype, respectively), negative in three cases (luminal A subtype) and weakly expressed in a single case (luminal A subtype); in ER negative category, CLDN3 expression was strong in four cases (one case of Her2/neu subtype and three cases of basal-like subtype), negative in two cases (normal breast-like subtype) and weak in five cases (one case of Her2/neu subtype, one triple-negative subtype, and three basal-like subtype). In Group 2, CLDN3 was overexpressed in 15 cases, histopathologically diagnosed as serous (10 cases), mucinous (two cases), endometrioid (two cases), and mixed carcinomas (one case); a weak expression was noticed in a single case, of the serous subtype; CLDN3 was undetectable in three cases (one serous, one clear cell, and one endometrioid type). Our comparative analysis of CLDN3 profile in breast and ovarian cancer clearly indicates organ specificity.