Down-regulation of the metastasis suppressor protein KAI1/CD82 correlates with occurrence of metastasis, prognosis and presence of HPV DNA in human penile squamous cell carcinoma

Abstract

In penile squamous cell carcinoma (PSCC), the outcome largely depends on early detection and resection of inguinal lymph node metastases. We investigated the role of metastasis suppressor protein kang ai 1 (KAI1)/cluster of differentiation 82 (CD82), which is known to be of prognostic significance for a wide variety of cancers. Moreover, we analysed the tumours for human papillomavirus (HPV) DNA and loss of heterozygosity at the 11p11.2 locus. Tissue samples of 30 primary PSCCs were investigated immunohistochemically using an anti-KAI1/CD82 polyclonal antibody. The expression was assessed according to the degree of KAI1/CD82-positive tumour cells as positive, decreased or negative. The presence of HPV6/11, HPV16 and HPV18 DNA was analysed by polymerase chain reaction. All patients with decreased or negative expression of KAI1/CD82 in primary lesions had lymph node metastases (p = 0.0002). Patients with positive KAI1/CD82 expression showed a significant better prognosis for survival compared to the other groups (p = 0.0042). Presence of HPV DNA was associated with decreased or negative KAI1/CD82 expression. Lacking or decreased expression of metastasis suppressor gene KAI1/CD82 appears to be a prognostic parameter for the occurrence of lymph node metastases in PSCC. Our study suggests an association of decreased KAI1/CD82 expression with tumour progression, development of metastases and disease-specific death.

Normal viability of Kai1/Cd82 deficient mice

“…Since this seminal discovery, KAI1 has been implicated in the metastatic spread of numerous cancer types. Reduced or lack of KAI1 expression in cancers is often linked with poor prognosis and its elevated expression is associated with a less severe clinical course [2][3][4][5][6][7][8][9][10][11][12][13].…”

Cancer penis evaluation of role of prophylactic inguinal lymph nodes dissection

“…23,24 15,24,25 And 5 years recurrence free rates reported 75 to 95 %. 26,27 Considering these facts we decided to adopt the aggressive approach of no observation in cases of non-palpable inguinal nodes and prophylactic lymph node dissection. Many reports shown improved survival.…”

Tetraspanins and tumor progression

“…In animal models, CD82 inhibits tumor metastasis, in the majority of reports, without affecting the proliferation of primary tumors [103,104,106,107,109,[111][112][113]. The forced expression of CD82 in prostate, breast, and liver cancer cells, as well as melanoma and fibroblatoma cells, significantly suppressed metastasis in spontaneous and/or experimental metastasis assays [103,111,[119][120][121].…”

“…CD82 level is inversely correlated with patient prognosis in a variety of solid tumors such as prostate, breast, colorectal, pancreatic, bladder, lung, oral, gastric, liver, esophageal, penile, and endometrial cancers [103,[109][110][111][112][113][114][115]. Notably, in breast cancer, CD82 expression is preferentially lost in estrogen receptor-positive tumors but constantly found in the primary and metastatic lesions of estrogen receptor-negative ones [116][117][118].…”