Expression of cadherins, p53, and BCL2 in small cell carcinomas of the cervix: Potential tumor suppressor role for N-cadherin

Abstract

Cadherins are tissue-specific cell adhesion molecules that function as tumor suppressors. Analysis of cadherin expression is useful for differentiation of tumor histogenesis, and because they serve as markers of tumor behavior and prognosis. Since the pattern of cadherin expression is not well characterized for small cell carcinoma of the cervix, we examined cases of these tumors for expression of cadherins, and two other oncoproteins p53 and BCL2. Four cases of small cell neuroendocrine carcinomas were identified from the Gynecologic Oncology Service with diagnoses confirmed by immunohistochemistry for neuroendocrine markers. Archival paraffin blocks were studied by heat-enhanced immunohistochemistry using commercially available antibodies specific for E-cadherin, P-cadherin, and N-cadherin, p53, and BCL2. Sections were examined for specific membrane staining of cadherins, nuclear staining of p53, and cytoplasmic staining of BCL2. E-cadherin was expressed in three of four cases, P-cadherin in one of four, and N-cadherin in none of four cases. P53 was expressed in one of four cases and BCL2 in one of four cases. The four cases showed three different patterns of immunohistochemical staining for the five oncoproteins. Specifically, two cases expressed E-cadherin only; one case lacked all three cadherins, was negative for BCL2, and was only positive for p53; and one case expressed E- and P-cadherin and BCL2. Prior studies of other neuroendocrine and small cell tumors of other organs showed E-cadherin expressed in 98% (42 /43), N-cadherin in 65% (28/43), and P-cadherin in 40% (17/43) of cases. Additionally, one case of vaginal small cell carcinoma showed expression of all three cadherins. The only significant difference between cervical primaries and other primary sites is that N-cadherin was not detected in our four cases vs. 65% expression in other sites (P < 0.001). We conclude that cadherin and oncoprotein profiles in small cell carcinoma of the cervix are different in the four cases analyzed. Additional cases need to be studied to determine the specificity and frequency of these oncoprotein profiles for small cell carcinoma of the cervix. These may possibly represent different oncogenic pathways in development of small cell cancer of the cervix. Also, our results suggest that N-cadherin may be a tumor suppressor gene in these tumors.