Immunohistochemical assessment of proliferating cell nuclear antigen in primary hepatocellular carcinoma and dysplastic nodules

Abstract

Conventional prognostic factors in primary hepatocellular carcinoma (HCC) include the TNM (tumornode-metastasis) system and the establishment of HCC grade (based on the cellular differentiation). Pathological and biological factors involved in HCC prognosis were also extensively studied. Thus, macroscopical and microscopical characteristics of the tumors are correlated with the survival of the patients and tumor recurrence. However, a complementary way of analysis of HCC prognosis is AbstractA complementary way for the assessment of HCC prognosis is represented by the analysis of molecular markers. Thus, immunohistochemical assessment of proliferation can describe tumor aggressiveness, probability of local recurrence or metastasis potential, being very useful for the assessment of recurrence-free survival and survival until death. The aim of our study was to assess proliferating cell nuclear antigen activity in HCC and dysplastic nodules as compared with surrounding nonneoplasic areas. Immunohistochemical techniques were thus performed on the samples obtained by ultrasound-guided liver biopsies or intraoperative biopsies, in 32 patients with HCC, as well as in 3 patients with dysplastic nodules ocurring in liver cirrhosis. Expression of PCNA within extranodular areas of the HCC patients in the absence or presence of cirrhosis, was increasing from 40% to 70%, respectively. PCNA expression further increased within intranodular areas of dysplastic nodules and HCC, to 100% and 96.88%, respectively. A progressive increase of the mean values of PCNA-LI was also observed from extranodular areas without or with cirrhosis, towards intranodular areas of dysplastic nodules and HCC (4.2%, 6.8%, 27.9%, 31.9%, respectively). Dysplastic nodules can thus be considered lesions with a high-proliferation rate, representing an early stage of hepatocarcinogenesis. This supported the current recommendations for borderline hepatocellular nodules identified by ultrasound, which indicate an aggressive treatment similar to malignant lesions. In summary, we demonstrated a progressively increasing rate of cellular proliferation, from extranodular non-neoplasic areas to intranodular areas (dysplastic nodules and HCC), as reflected by an increased expression of proliferating cell nuclear antigen labelling index.

Expression of p57kip2and its relationship with clinicopathology, PCNA and p53 in primary hepatocellular carcinoma

“…PCNA was an assistant factor of DNA synthetase delta, it took part in DNA biological synthesis and regulated cell cycle and cell proliferation by a tetramer with cyclin, CDK and p21. The amount of PCNA could reflect the proliferating activity of cancer cells, and could be regarded as the index of proliferation [21] . Over-expression of PCNA was associated with a variety of tumors of the digestive system.…”

Effects of Gastric Vagotomy on Visceral Cell Proliferation Induced by Ventromedial Hypothalamic Lesions: Role of Vagal Hyperactivity

“…Stomach specimens were also subjected to combined hematoxylin-eosin and immunostaining using an anti-PCNA antibody (1:1,000, Dako, Kyoto, Japan) as a marker of cell proliferation (Hall et al 1990). The mitotic index (number of cells with PCNA-positive nuclei out of 1,000 nuclei :‰) was determined in individual specimens (Saftoiu et al 2003).…”

Comparative proteomic analysis of mouse livers from embryo to adult reveals an association with progression of hepatocellular carcinoma

“…Five of the studied fetal genes (hASB4, hPCNA, hIF5A, hHSP7C, and hHEM6) show induced expression in metastatic HCC cell lines. Proliferating cell nuclear antigen (PCNA) has been shown previously to be one of the molecules associated with the advanced stages of HCC and its malignant status [29,30]. The expression of another fetal protein, HSP7C (heat shock cognate 71-kDa protein), a member of heat shock protein family, was found to be significantly up-regulated in HCC [31].…”