Proliferative and apoptotic activity in hepatocellular carcinoma and surrounding non-neoplastic liver tissue

Pižem, Jože; Marolt, Vera Ferlan; Luzar, Boštjan; Cör, Andrej

doi:10.1007/s004240100014

Cited by 25 publications

(24 citation statements)

References 5 publications

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“…The median tumor size was 4.5 cm (range 0. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]; the mean tumor size 5.574.4 cm. In total, 72% of the hepatocellular carcinoma were solitary tumors, 28% multiple.…”

Section: Resultsmentioning

confidence: 99%

“…13 Thus, mean proliferation labeling index (Ki-67, Proliferation Cell Nuclear Antigen) is shown to correlate significantly with survivin, whereas apoptotic index (single-stranded DNA immunohistochemistry, Tunel) does not. [13][14][15][16] This suggests that, as in hepatocellular carcinoma, the prognostic significance in other cancers of survivin immunostain in nuclei relates to its cell cycle, and not to its cytoplasmic antiapoptotic, effect. Moon and Tarnawski 32 suggest that cytoplasmic localization of survivin in quiescent nonmalignant cells suppresses apoptosis, while its nuclear translocation in hepatocellular carcinoma may be important in regulation of proliferation and differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…13 In human hepatocellular carcinoma, nuclear survivin by immunofluorescence and immunohistochemistry strongly correlated with proliferation index (Proliferation Nuclear Cell Antigen) although not with apoptotic index (Tunel method). 13,14 In other studies, 12,15,16 survivin messenger RNA (mRNA) quantitated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) (divided by amount of glyceraldehyde-3-phosphate dehydrogenase [GAPDH] mRNA to obtain normalized amounts of transcripts), correlated significantly with proliferation (MIB-1), but with a significant negative correlation with apoptotic index (single-stranded DNA).…”

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Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome

et al. 2004

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Survivin is a novel inhibitor of apoptosis. It is detected in fetal and neoplastic adult tissue, but not in normal tissues. Several recent studies have shown that survivin not only inhibits apoptosis, but also accelerates cancer cell proliferative activity. Expression of the protein may be of prognostic significance and therapeutic relevance in many cancers. We investigated survivin expression in hepatocellular carcinoma, correlating results with proliferation (MIB-1), prognostic factors, and outcome. Paraffin-embedded sections of 72 hepatocellular carcinoma were immunostained for survivin and MIB-1 using tissue microarray technology. Expression was evaluated in nuclei and cytoplasm as intensity (0-3 þ ), and percentage of positive cells scored on a four-tiered system with less than 10% ¼ negative; 10-25% ¼ 1; 26-50% ¼ 2; 51-75% ¼ 3; and 76-100% ¼ 4. Frequency of nuclear survivin expression was 43%. There was a significant correlation between nuclear survivin expression and nuclear grade (P ¼ 0.0271), microvascular invasion (P ¼ 0.0064), mitotic rate (P ¼ 0.0017), and MIB-1 (P ¼ 0.0001), as well as local recurrence (P ¼ 0.0487), and disease-free survival (P ¼ 0.0098). Histologic grade (P ¼ 0.0544) and stage (P ¼ 0.0548) tended to correlate with survivin expression, which did not correlate with cirrhosis, tumor necrosis, multiple tumors, metastatic disease, or overall survival. Survivin expression correlates with poor prognostic parameters (high nuclear and histologic grade, microvascular invasion, increased proliferation (mitotic count, MIB-1)), local recurrence, and shorter diseasefree survival, but does not correlate with overall survival. An important role is suggested for survivin in progression, recurrence, and treatment of hepatocellular carcinoma.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome

et al. 2004

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“…PCNA is a protein involved in DNA replication and repair in dividing cells. Ki67 is a prototypic cell cycle-related nuclear protein expressed only in proliferating cells [33]. Only the cells in group 1a organs were able to upregulate the expression of both proteins 24 h after resection as shown in Figs.…”

Section: Discussionmentioning

confidence: 95%

Extended liver resection after preoperative chemotherapy: influence on regeneration and endoplasmic reticulum stress response

Manekeller

Seinsche

Sioutis

et al. 2008

Langenbecks Arch Surg

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“…These differences reflect probably sampling errors and size of the biopsies, but they do not seem to indicate a significant difference between the results [4]. Recent studies also suggested that apoptosis is slightly higher in HCC as compared to normal liver, which implies that it is less involved in the development and progression of this disease [11][12][13]. Thus, although a high index of proliferation seems to be characteristic for HCC, this is not associated with an increased rate of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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

Săftoiu¹,

Ciurea²,

Georgescu

et al. 2003

J Cellular Molecular Medi

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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.

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Proliferative and apoptotic activity in hepatocellular carcinoma and surrounding non-neoplastic liver tissue

Cited by 25 publications

References 5 publications

Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome

Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome

Extended liver resection after preoperative chemotherapy: influence on regeneration and endoplasmic reticulum stress response

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

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