PMID- 27468214 OWN - NLM STAT- MEDLINE DCOM- 20170413 LR - 20211203 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 22 IP - 27 DP - 2016 Jul 21 TI - Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases. PG - 6246-56 LID - 10.3748/wjg.v22.i27.6246 [doi] AB - AIM: To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC). METHODS: In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases. The protein products of genes known to be involved in molecular pathogenesis of HCC, including epidermal growth factor receptor (EGFR), MET, keratin 19 (K19), vimentin, beta-catenin, mechanistic target of rapamycin (mTOR), extracellular signaling-related kinase (ERK)1, ERK2, Ki67, cyclin D1, caspase 3 and p53, were detected by immunohistochemistry on tissue microarrays. The expression levels were scored and statistically assessed for correlation with HCC parameters. RESULTS: Infection with hepatitis C virus was identified in 49% of the 80 autopsy patients, cirrhosis in 90%, advanced tumors in 95%, and extrahepatic metastases in 38%. Expression of K19, p53 and ERK1 correlated to high-grade lesions. Expression of ERK1, nuclear beta-catenin, cyclin D1 and ERK2 correlated to higher rates of cell proliferation as determined by Ki67. Expression of MET, EGFR (> 0) and caspase 3 correlated with lower histological grades. Expression of EGFR correlated to that of caspase 3, and overexpression of EGFR (>/= 200/300) was observed in low-grade tumors more frequently (grades 1 and 2: 67% vs grade 3: 27% and grade 4: 30%). Expression of ERK1 was associated with that of K19 and vimentin, whereas expression of ERK2 was associated with that of cyclin D1, MET and membrane beta-catenin. Expression of vimentin was strongly correlated with that of K19. CONCLUSION: Expression of K19, p53, ERK1, ERK2, vimentin and nuclear beta-catenin was related to higher-grade markers, as opposed to expression/overexpression of EGFR, MET and caspase 3. FAU - Felipe-Silva, Aloisio AU - Felipe-Silva A AD - Aloisio Felipe-Silva, LIM 14-Patologia Hepatica, Faculdade de Medicina da USP, 01246-903 Sao Paulo SP, Brazil. FAU - Wakamatsu, Alda AU - Wakamatsu A AD - Aloisio Felipe-Silva, LIM 14-Patologia Hepatica, Faculdade de Medicina da USP, 01246-903 Sao Paulo SP, Brazil. FAU - Dos Santos Cirqueira, Cinthya AU - Dos Santos Cirqueira C AD - Aloisio Felipe-Silva, LIM 14-Patologia Hepatica, Faculdade de Medicina da USP, 01246-903 Sao Paulo SP, Brazil. FAU - Alves, Venancio Avancini Ferreira AU - Alves VA AD - Aloisio Felipe-Silva, LIM 14-Patologia Hepatica, Faculdade de Medicina da USP, 01246-903 Sao Paulo SP, Brazil. LA - eng PT - Journal Article PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (CCND1 protein, human) RN - 0 (Keratin-19) RN - 0 (Ki-67 Antigen) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Vimentin) RN - 0 (beta Catenin) RN - 136601-57-5 (Cyclin D1) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.24 (MAPK1 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Autopsy MH - Brazil MH - Carcinoma, Hepatocellular/classification/epidemiology/*metabolism/pathology MH - Case-Control Studies MH - Caspase 3/metabolism MH - Cross-Sectional Studies MH - Cyclin D1/metabolism MH - ErbB Receptors/metabolism MH - Female MH - HIV Infections/epidemiology MH - Hepatitis B, Chronic/epidemiology MH - Hepatitis C, Chronic/epidemiology MH - Humans MH - Immunohistochemistry MH - Keratin-19/metabolism MH - Ki-67 Antigen/metabolism MH - Liver Cirrhosis/epidemiology/pathology MH - Liver Neoplasms/classification/epidemiology/*metabolism/pathology MH - Male MH - Middle Aged MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Proto-Oncogene Proteins c-met/metabolism MH - Retrospective Studies MH - TOR Serine-Threonine Kinases/metabolism MH - Tissue Array Analysis MH - Tumor Suppressor Protein p53/metabolism MH - Vimentin/metabolism MH - beta Catenin/metabolism PMC - PMC4945983 OTO - NOTNLM OT - Autopsy OT - Classification OT - Epidermal growth factor receptor OT - Hepatocellular carcinoma OT - Immunohistochemistry OT - Liver EDAT- 2016/07/29 06:00 MHDA- 2017/04/14 06:00 PMCR- 2016/07/21 CRDT- 2016/07/29 06:00 PHST- 2016/03/22 00:00 [received] PHST- 2016/05/19 00:00 [revised] PHST- 2016/06/15 00:00 [accepted] PHST- 2016/07/29 06:00 [entrez] PHST- 2016/07/29 06:00 [pubmed] PHST- 2017/04/14 06:00 [medline] PHST- 2016/07/21 00:00 [pmc-release] AID - 10.3748/wjg.v22.i27.6246 [doi] PST - ppublish SO - World J Gastroenterol. 2016 Jul 21;22(27):6246-56. doi: 10.3748/wjg.v22.i27.6246.