Abstract
BackgroundAberrant expression of P-cadherin has been reported in various cancers, and has been attracting attention as a target for cancer treatment. Ovarian cancer, the leading cause of death among gynecologic malignancies, is classified into four histological subtypes: serous, mucinous, endometrioid, and clear cell, and each has distinct biological behavior. Although a negative survival impact in serous ovarian cancer patients and some functional role in peritoneal dissemination have been reported, differences of P-cadherin expression in histological subtypes and the proportion and distribution of positive cells remain to be investigated. The aims of this study were to clarify the histological and distributional profiles of P-cadherin expression in ovarian cancer for development of target-therapy in near future.MethodsA total of 162 primary, 60 metastatic, and 8 recurrent tumors (all cases from 162 ovarian cancer patients) were enrolled in the study. Immunohistochemistry was performed for P-cadherin expression. Associations with clinicopathological characteristics and survival were analyzed.ResultsP-cadherin expression showed a strong correlation with the FIGO stage, histological subtypes, positive peritoneal dissemination (P < 0.01), positive distant metastasis (P < 0.05), and trend toward negative overall survival probability (P = 0.050). P-cadherin was intensely and broadly expressed in mucinous, endometrioid, and serous subtypes (P < 0.01). Disseminated tumors demonstrated similar P-cadherin expression to primary tumors whereas metastatic lymph nodes demonstrated significantly decreased expression (P < 0.01).ConclusionsMucinous, endometrioid, and serous ovarian cancer patients accompanied with peritoneal disseminations are the most potent candidates for P-cadherin targeted drug delivery strategies. P-cadherin-targeted therapy may benefit and improve survival of poor-prognosis populations.
Highlights
Aberrant expression of P-cadherin has been reported in various cancers, and has been attracting attention as a target for cancer treatment
60–70% of patients are detected in an advanced stage at the time of diagnosis, because ovarian cancer rarely disseminates through the vasculature but has a tendency to metastasize to the peritoneum, unlike many other types of solid tumors [2] [3]
P-cadherin expression is strongly correlated with histologic subtype and progressive clinicopathological features of ovarian cancer We investigated the association between P-cadherin expression and clinicopathological features of ovarian cancer using Immunohistochemical staining (IHC) in 162 patients with ovarian cancer
Summary
Aberrant expression of P-cadherin has been reported in various cancers, and has been attracting attention as a target for cancer treatment. 60–70% of patients are detected in an advanced stage (stages III and IV) at the time of diagnosis, because ovarian cancer rarely disseminates through the vasculature but has a tendency to metastasize to the peritoneum, unlike many other types of solid tumors [2] [3] These patients with peritoneal dissemination at diagnosis have a 5-year survival rate of less than 30% and a very high recurrence rate even with a successful response to surgery or chemotherapy [1] [2] [4]. Besides its regulatory role in implantation, embryo morphogenesis, cellular homeostasis, cell differentiation, cell shape, cell polarity, and growth and migration in fetal development [8] [9] [10], aberrant expression in various cancers has been reported Since it is only faintly expressed in limited organs of normal adult tissue, it has been attracting attention as a therapeutic target
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