Hepatocyte growth factor, transforming growth factor alpha, and their receptors as combined markers of prognosis in hepatocellular carcinoma.

A change in the balance between proliferation and apoptosis in the course of hepatocellular carcinoma (HCC) development and progression has been suspected. We wanted to identify related genes whose mRNA levels could provide markers of severity and prognosis after resection. The extent of cell apoptosis, proliferation, and differentiation was measured with a terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate-biotin nick-end labeling assay, and the Ki-67 index was determined in paired tumor and cirrhotic tissue samples from patients who had undergone HCC resection after diagnosis of hepatitis C-related or alcoholism-related cirrhosis. These patients included two groups with highly versus poorly differentiated tumor cells, and the latter was split into two subgroups of those with versus without early recurrence. The mRNA levels for various apoptosis-related or proliferation-related genes and those for the growth factor/receptor systems were measured by quantitative reverse transcriptase-polymerase chain reaction in paired tumor and cirrhotic liver samples from every patient, and some of the corresponding proteins were detected by immunohistochemistry. In all instances, protein expression was highly heterogeneous within groups and similar between groups. In contrast, some differences in mRNA level between tumor and cirrhotic tissues were quite informative. Low levels of hepatocyte growth factor and transforming growth factor alpha mRNAs were found concomitantly in highly differentiated tumors, whereas overexpression of mRNAs for the cognate receptors c-met and epidermal growth factor receptor were found in poorly differentiated tumors and primarily in patients with early tumor recurrence. These results argue for growth factor-dependent HCC development and provide novel and combined prognosis markers after HCC surgery.

[Detection of HHV8 latent nuclear antigen by immunohistochemistry. A new tool for differentiating Kaposi's sarcoma from its mimics]. / Détection de l'antigène LNA1 de l'HHV8 par immunohistochimie.

UNLABELLED: The purpose of this work was to study the value of HHV8 latent nuclear antigen 1 detection by immunohistochemistry in Kaposi sarcoma and its mimics. MATERIALS AND METHODS: : We used the mAB LNA53 against the latent nuclear antigen 1 of HHV8 to study its expression by immunohistochemistry in paraffin embedded biopsy of Kaposi and its mimics. We also performed in vitro PCR for HHV8 DNA, extracted from the same paraffin embedded biopsies. We studied characteristic lesions of 26 Kaposi sarcoma; 20 cutaneous lesions raising problems of differential diagnosis. We also studied 11 biopsies of skin, mucosa, or lymph nodes of patients infected by HHV8 but without Kaposi sarcoma, and 22 lesions initially classified by histological analysis as uncertain Kaposi sarcoma . RESULTS: : In all cases of Kaposi, HHV8 was detected in the majority of tumor cells, with no expression in other adjacent cells. In these biopsies HHV8 DNA, was identified by in vitro PCR. None of the 20 Kaposi sarcoma mimics and the 11 lesions of patients infected by HHV8 but without any Kaposi sarcoma, were HHV8+ on immunohistochemistry sections or by PCR. From the 22 cases of uncertain Kaposi sarcoma, only the 14 lesions HHV8 PCR+ and with a clinical evolution in accordance with a Kaposi sarcoma, were HHV8+ on immunohistochemistry. In contrast, the 8 cases negative for HHV8 on immunohistochemistry were also PCR- and had a self-healing evolution in accordance with the diagnostic of pyogenic granuloma. CONCLUSION: : Detection of the latent nuclear antigen 1 of HHV8 by immunohistochemistry is a specific and sensitive diagnostic tool for differentiating Kaposi sarcoma from its mimics.