Combination of hepatocellular markers is useful for prognostication in gastric hepatoid adenocarcinoma

Mikako Osada; Shinichi Aishima; Minako Hirahashi; Nobuyoshi Takizawa; Shunsuke Takahashi; Kazuhiko Nakamura; Masao Tanaka; Yoshihiko Maehara; Ryoichi Takayanagi; Yoshinao Oda

doi:10.1016/j.humpath.2014.02.003

Combination of hepatocellular markers is useful for prognostication in gastric hepatoid adenocarcinoma

Hum Pathol. 2014 Jun;45(6):1243-50. doi: 10.1016/j.humpath.2014.02.003. Epub 2014 Feb 20.

Affiliations

¹ Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
² Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
³ Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
⁴ Department of Surgery and Medical Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
⁵ Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: oda@surgpath.med.kyushu-u.ac.jp.

PMID: 24767858
DOI: 10.1016/j.humpath.2014.02.003

Abstract

Hepatoid or α-fetoprotein (AFP)-producing adenocarcinomas of stomach growing in a solid pattern are highly aggressive tumors. It is difficult to detect hepatoid differentiation solely based on findings from hematoxylin and eosin stainings, especially in small biopsy specimens. Gastric adenocarcinomas with hepatoid differentiation should be distinguished from solid-type gastric adenocarcinoma because of their different biological behavior. We immunohistochemically analyzed hepatocellular markers (AFP, glypican 3, and Hepatocyte paraffin 1 [HepPar-1]) and possible markers of gastric hepatoid adenocarcinoma (Sal-like protein 4 [SALL4] and palate, lung, and nasal epithelium carcinoma-associated protein [PLUNC]) to detect hepatoid differentiation in 45 gastric hepatoid adenocarcinomas and 47 nonhepatoid solid-type poorly differentiated adenocarcinomas. There were a higher incidence of vascular invasion (P = .0055) and distant metastasis (P = .0458) in hepatoid adenocarcinoma than in nonhepatoid adenocarcinoma. AFP, SALL4, HepPar-1, and glypican 3 were significantly higher in hepatoid adenocarcinoma than in nonhepatoid adenocarcinoma. All 5 markers were positive in both the hepatoid/solid and the tubular component. In hepatoid adenocarcinoma, the frequency of distant metastasis was significantly higher in SALL4-negative cases than in SALL4-positive cases (P = .0381). HepPar-1 was associated with liver metastasis (P = .0452). PLUNC was correlated with lymph node metastasis (P = .0375). There was a significant difference in the survival rate between HepPar-1-positive and HepPar-1-negative groups (P = .0437). The coexpression of PLUNC and SALL4 and the other coexpression of HepPar-1 and PLUNC were associated with poorer prognosis (P = .0181 and P = .0443, respectively). AFP, SALL4, HepPar-1, and glypican 3 are useful for the detection of hepatoid differentiation. A combination of PLUNC, HepPar-1, and SALL4 could be a reliable prognostic indicator in hepatoid adenocarcinoma of the stomach.

Keywords: HepPar-1; Hepatoid adenocarcinoma; PLUNC; SALL4; Solid.

MeSH terms

Adenocarcinoma / metabolism*
Adenocarcinoma / mortality
Adenocarcinoma / pathology*
Aged
Biomarkers, Tumor / analysis*
Female
Hepatocytes / pathology
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Middle Aged
Prognosis
Stomach Neoplasms / metabolism*
Stomach Neoplasms / mortality
Stomach Neoplasms / pathology*

Substances

Biomarkers, Tumor