[Conventional grading vs. molecular grading : Decision aids for clinical routine]. / Konventionelles vs. molekulares Grading : Entscheidungshilfen für den klinischen Alltag.

Conventional histopathological grading of a cancer is of utmost importance for the management and prognosis of the patient. Histopathological grading is predominantly a function of the differentiation and proliferation of tumor cells, the amount of necrosis present and the pattern of invasion. In addition, the molecular set-up of a given cancer which can be determined to some degree by immunohistochemistry or by methods analyzing genetic and epigenetic alterations can be used in some instances to improve the information gained by conventional histopathologic grading. Indeed, this latter option implies the promise of individualized tumor therapy. While this promise is on the horizon, the clinical implications for penile cancer are not yet transferable to individualized penile cancer treatment.

The role of annexins I, II and IV in tumor development, progression and metastasis of human penile squamous cell carcinomas.

PURPOSE: The outcome of patients with penile squamous cell carcinomas (PSCC) largely depends on occurrence of metastasis. Therefore, prognostic markers indicating the risk for tumor cell spreading would be useful. Since Annexins are potential prognostic markers in a variety of tumors, we immunohistochemically examined the expression of Annexins I, II and IV (ANX AI, ANX AII and ANX AIV) in PSCC. METHODS: Samples originated from 29 patients subjected to surgical resection of invasive PSCC. Immunohistochemistry was done on paraffin-embedded sections using monoclonal antibodies against ANX AI, ANX AII and ANX AIV. Expression of ANXs was compared with clinical data. RESULTS: ANX AI expression was found in conventional PSCC and was absent in basaloid and sarcomatoid subtypes. High ANX AI score was significantly associated with higher T stages (P = 0.006). Strong expression in the invasion front of carcinomas was significantly associated with the occurrence of lymph node metastasis (P = 0.001). ANX AIV expression was weak in conventional PSCC, while it was strong in basaloid and sarcomatoid subtypes. Strong expression of Annnexin IV in the invasion front also showed a significant association with metastasis (P = 0.019). CONCLUSION: Expression of ANXs was different in histologic subtypes of penile carcinomas. Strong expression of ANX AI and ANX AIV in the invasion front seems to indicate a higher risk of lymph node metastasis.

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.

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.