Claudin-10 is a new candidate prognostic marker in metastatic high-grade serous carcinoma

Abstract

The objective of this study was to analyze the expression and prognostic role of the gap junction protein claudin-10 in high-grade serous carcinoma (HGSC). Claudin-10 protein expression by immunohistochemistry was analyzed in 588 HGSC (414 effusions, 174 surgical specimens). Expression in mesotheliomas (n = 97; 47 effusions, 50 surgical specimens) was studied for comparative purposes. CLDN10 mRNA expression by quantitative RT-PCR (qRT-PCR) was analyzed in 40 HGSC effusions. Claudin-10 protein expression was found in 360/588 (61%) HGSC vs. 19/97 (20%) mesotheliomas (p < 0.001), and was higher in HGSC surgical specimens compared to effusions (p < 0.001). qRT-PCR confirmed the presence of CLDN10 mRNA in HGSC effusions. High (> 25%) claudin-10 expression in HGSC effusions was significantly associated with shorter overall survival (OS; p = 0.036) and progression-free survival (PFS; p = 0.045) in univariate analysis, and was an independent prognosticator of OS in multivariate analysis (p = 0.045). In conclusion, claudin-10 protein expression is higher in HGSC compared to mesothelioma, although the diagnostic power of this marker appear to be lesser than other claudin family members. Claudin-10 expression in HGSC effusions is marker of more aggressive disease.

Occludin is overexpressed in tubo-ovarian high-grade serous carcinoma compared to mesothelioma and is a marker of tumor progression and chemoresistance

“…In the present study, occludin was significantly overexpressed in HGSC compared to mesothelioma specimens and was absent in reactive mesothelial cells, suggesting a potential diagnostic role. This finding is in full agreement with our previous reports with respect to claudins in these two malignancies [ 6 , 7 ]. Whether occludin is differentially expressed in epithelioid and sarcomatoid mesothelioma cannot be resolved in the present study, as the vast majority of cases, including all effusions, had epithelioid differentiation.…”

“…We recently studied the expression of claudin-10, another tight junction protein, in this cohort [ 6 ]. Statistical analysis showed significant association between expression of these proteins in 391 HGSC effusions immunostained for both (p < 0.001; mean rank = 161.95 vs. 207.23 for the low and high occludin expression group, respectively).…”

“…Seen together with the overexpression of E-cadherin [ 10 ] and claudins [ 8 ] in effusions, a unique anatomic compartment, compared to solid tumors, HGSC cells are likely to be undergoing MET when present in the anoikis-resistant growth conditions of serous effusions, as previously reported by our group [ 17 ]. Of note, occludin and claudin-10 were significantly co-expressed in HGSC effusions, in staining of serial sections from the same cell block, despite the fact that the latter was under-expressed rather than over-expressed in effusions compared to surgical specimens [ 6 ], suggesting that their co-expression may provide survival advantage in the effusion microenvironment.…”

“…The hypothesis linking occludin to chemotherapy resistance is supported by another observation in the present study, i.e., the association between expression of this protein in surgical HGSC specimens and poor chemoresponse at diagnosis, a continuous variable, as well as intrinsic chemoresistance, a dichotomous variable with cut-off at 6 months. In our previous study of claudin-10, higher expression of this protein was found in surgical specimens obtained following neoadjuvant chemotherapy compared to chemo-naïve tumors [ 6 ]. Thus, the findings of both studies suggest that higher expression of tight junction proteins is related to tumor progression and aggressive disease in HGSC.…”