The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection

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Abstract

Background

The expression of CK19 in primary hepatocellular carcinoma (HCC) is associated with a poor outcome. However, few studies have investigated the expression profile of CK19 in regional lymph nodes (LNs) of HCC after hepatic resection. The purpose of this study was to evaluate the expression of CK19 in primary liver tumor and regional LNs of HCC with and without lymph node metastasis (LNM).

Methods

The expression of CK19 in patients with (n = 16) and without LNM (n = 26) was examined using immunohistochemical staining. Both the primary tumor and LN specimen were studied for their CK19 expression. Clinico-pathological variables and prognostic significance were analyzed.

Results

Immunopositivity of CK19 in primary liver tumor was significantly correlated with LNM ( P = 0.005) and tumor non-encapsulation ( P <0.005). Univariate analysis showed that CK19 expression in primary liver tumor, CK19 expression in regional LN, vascular invasion, daughter nodules, positive resection margin and American Joint Committee on Cancer (AJCC) tumor stage significantly decreased overall survival. Multivariate analysis demonstrated that daughter nodules ( P = 0.001) and CK19 expression in regional LN ( P = 0.002) were independent prognostic factors for overall survival.

Conclusions

This study showed that CK19 expression in regional LN of HCC was associated with LNM and an extremely poor outcome after operation. It is of clinical significance to identify these patients at risk for more aggressive HCC, and multi-modality treatment could be helpful to improve their dismal outcome.

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Most cited references 33

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Molecular classification and novel targets in hepatocellular carcinoma: recent advancements.

Sara Toffanin, Josep Llovet, Beatriz Minguez … (2010)

Hepatocellular carcinoma (HCC) is one of most lethal cancers worldwide. Strategic decisions for the advancement of molecular therapies in this neoplasm require a clear understanding of its molecular classification. Studies indicate aberrant activation of signaling pathways involved in cellular proliferation (e.g., epidermal growth factor and RAS/mitogen-activated protein kinase pathways), survival (e.g., Akt/mechanistic target of rapamycin pathway), differentiation (e.g., Wnt and Hedgehog pathways), and angiogenesis (e.g., vascular endothelial growth factor and platelet-derived growth factor), which is heterogeneously presented in each tumor. Integrative analysis of accumulated genomic datasets has revealed a global scheme of molecular classification of HCC tumors observed across diverse etiologic factors and geographic locations. Such a framework will allow systematic understanding of the frequently co-occurring molecular aberrations to design treatment strategy for each specific subclass of tumors. Accompanied by a growing number of clinical trials of molecular targeted drugs, diagnostic and prognostic biomarker development will be facilitated with special attention on study design and with new assay technologies specialized for archived fixed tissues. A new class of genomic information, microRNA dysregulation and epigenetic alterations, will provide insight for more precise understanding of disease mechanism and expand the opportunity of biomarker/therapeutic target discovery. These efforts will eventually enable personalized management of HCC.

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Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence.

Masao Ogawa, Takahiro Uenishi, Kazuhiro Hirohashi … (2003)

Clinicopathologic features and postoperative outcomes were investigated for patients who underwent curative surgery for biliary marker (CK7 and CK19)-positive hepatocellular carcinoma (HCC). Of 157 HCCs, 93 were CK7(-)CK19(-), 49 were CK7(+)-CK19(-), 1 was CK7(-)CK19(+), and 14 were CK7(+)- CK19(+). Semiquantitative analysis of expression levels demonstrated a significant correlation between CK7 and CK19 expression. Of various clinicopathologic parameters, tumor differentiation exhibited a significant correlation with CK7 and CK19 expression. All 15 patients with CK19-positive HCC also had anti-HBc. Log-rank test revealed that CK7 expression, CK19 expression, high aspartate aminotransferase (AST) activity, low albumin concentration, portal invasion, intrahepatic metastasis, and severe fibrosis (cirrhosis) reduced the tumor-free survival rate. Multivariate analysis demonstrated that CK19 expression, intrahepatic metastasis, and severe fibrosis were independent predictors of postoperative recurrence, while CK7 expression was not. Twelve of 15 patients with CK19-positive HCC had tumor recurrence within 2 years after surgery, a significantly higher incidence of early recurrence than for CK19-negative HCC. The incidence of extrahepatic disease, especially lymph node metastasis, was significantly higher for patients with CK19-positive HCC. These findings indicate that CK19 expression is a predictor of early postoperative recurrence due to increased invasiveness.

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Hepatic OV-6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man.

T Roskams, R. De Vos, P Van Eyken … (1998)

Since in rat experiments, activation of progenitor cells is seen in conditions associated with hepatocyte injury or inhibited replication, we compared the activation and fate of human putative progenitor cells in regenerating liver versus chronic cholestatic disease, using immunohistochemistry, rat oval cell marker OV6 and a panel of bile ductular cell markers. We compared the results with different rat models: the choline-deficient acetylaminofluorene (CDAAF)- and alpha-naphthylisothiocyanate (ANIT)-model, using immunohistochemistry and electron microscopy. In very early stages of human liver regeneration, putative progenitor cells in the vicinity of portal tracts were immunoreactive for OV6, CK7, CK19 and chrom-A. In later stages of regeneration and in chronic cholestasis, reactive bile ductules (immunoreactive for OV6, CK7, CK19, chrom-A, NCAM) and intermediate hepatocyte-like cells (immunoreactive for OV6, CK7, chrom-A), became apparent, suggesting bidirectional differentiation of the putative progenitor cells. In regenerating human liver, intermediate hepatocyte-like cells became more numerous with time and extended far into the lobule. In advanced cholestasis, intermediate hepatocyte-like cells were less numerous and formed periportal rosettes and small clusters. In the CDAAF rat model (associated with inhibited hepatocyte replication), but not in the ANIT model, gradual differentiation of oval cells into hepatocytes was seen after stopping the diet. Our results in human liver suggest that reactive ductules and intermediate hepatocyte-like cells originate at least partly from activation and differentiation of "progenitor cells". In regeneration after submassive necrosis, in analogy with what is seen in rat models, differentiation towards hepatocytes is more pronounced than in chronic cholestasis.

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Author and article information

Journal

Journal ID (nlm-ta): World J Surg Oncol

Journal ID (iso-abbrev): World J Surg Oncol

Title: World Journal of Surgical Oncology

Publisher: BioMed Central

ISSN (Electronic): 1477-7819

Publication date Collection: 2013

Publication date (Electronic): 12 June 2013

Volume: 11

Page: 136

Affiliations

[1 ]The Department of Surgery, Chang Gung Memorial Hospital, No 5 Fusing Street, Taoyuan County, Gueishan 333, Taiwan

[2 ]The Department of Pathology, Chang Gung Memorial Hospital, No 5 Fusing Street, Taoyuan County, Gueishan 333, Taiwan

[3 ]Chang Gung University, 259 Wen-Hwa 1st Road, Taoyuan, Kuei-Shan 333, Taiwan

[4 ]Graduate Institute of Clinical Medical Sciences, Chang Gung University, 259 Wen-Hwa 1st Road, Taoyuan, Kuei-Shan 333, Taiwan

Article

Publisher ID: 1477-7819-11-136

DOI: 10.1186/1477-7819-11-136

PMC ID: 3708812

PubMed ID: 23758804

SO-VID: 5e408be1-3030-482d-82cc-04e4a2b0cf7f

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 12 September 2012

Date accepted : 1 June 2013

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The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection

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Abstract

Background

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Conclusions

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Karger: Oncology

Most cited references 33

Molecular classification and novel targets in hepatocellular carcinoma: recent advancements.

Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence.

Hepatic OV-6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man.

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