Histogenesis of hepatoid adenocarcinoma of the stomach:Molecular evidence of identical origin with coexistent tubular adenocarcinoma

Abstract

Hepatoid adenocarcinoma of the stomach is a highly malignant neoplasm. Most gastric hepatoid adenocarcinomas coexist with tubular adenocarcinoma. However, the relationship between hepatoid adenocarcinoma and tubular adenocarcinoma is still unclear. In the present study, the characteristics of the coexistent tubular adenocarcinomas were determined by examining their profiles of mucin production. Subsequently, molecular pathological techniques were applied to determine the clonality of 15 mixed hepatoid and tubular adenocarcinomas of the stomach. Mucin analysis suggested that the coexistent tubular adenocarcinomas with hepatoid adenocarcinoma were of the intestinal type. The patterns of chromosome X inactivation were identical between the hepatoid adenocarcinoma component and tubular adenocarcinoma component in all of 3 informative female cases. Mutations in the p53 gene were found in 5 cases. The sequences were identical within both tumor components in all 5 cases. Microsatellite analysis indicated more than 3 common patterns of loss of heterozygosity in 8 cases. These observations strongly suggested that hepatoid adenocarcinomas were of identical origin to coexistent tubular adenocarcinomas.

Hepatoid Adenocarcinoma – Review of the Literature Illustrated by a Rare Case Originating in the Peritoneal Cavity

“…Oftheothertumourmarkers,especiallyCEAisoftenproducedbyHAC.PositivityforCEAwasobservedin50-100% of all published cases, occurring in all HAC of the pancreas [27,28],ovaries,andfallopiantube [21,[29][30][31][32][33][34][35][36],in86%ofthe gallbladdercases [10,22,23,37,38],andin51%ofthegastric HAC [7,8,10,11,24]. Our patient had normal CEA serum concentrations,butthetumourcellswereweaklystainedby CEAinconcordancewiththeotherpublishedHACcaseof theperitonealcavity [15].Noticeablefordiagnosticreasonsis thepositivityforCEA,AFP,andCA125orthedetectionof elevatedserumlevelsofCA125inovarianHAC [21,29,[31][32][33][34][35][36].TheCEAstainingis,however,oflittlevaluefordifferentiationbetweenHACandHCC,asthemajorityofHCCare alsoCEA-positive [39].…”

Hepatoid adenocarcinoma of the stomach: histogenesis and progression in association with intestinal phenotype

“…Kishimoto and associates [6] suggested that HAC develops from tubular or papillary adenocarcinoma, which tends to be detected superficially in the tumor. Akiyama and coworkers [7] found the adenocarcinomatous and hepatoid components to be of monoclonal origin, with identical patterns of genetic alteration. In addition, those investigators analyzed the cellular phenotype of these tumors using mucin histochemical methods and found that the adenocarcinomatous components expressed the intestinal phenotype.…”

“…In addition, those investigators analyzed the cellular phenotype of these tumors using mucin histochemical methods and found that the adenocarcinomatous components expressed the intestinal phenotype. However, no mention was made of the cellular mucin phenotype of the hepatoid components [7]. Analysis of the cellular phenotype is considered useful for understanding the genesis and biological behavior of tumors [8][9][10].…”

Variants of Gastric Carcinoma: Morphologic and Theranostic Importance

“…Kishimoto et al proposed that gastric carcinoma might acquire hepatic differentiation during the tumor progression, "HACS transdifferentiation" [56]. Akiyama et al demonstrated that the hepatoid component exhibited exactly same patterns of chromosome X inactivation, p53 gene mutation, the level of p53 expression, and loss of heterozygosity with conventional adenocarcinomatous component of HACS [57]. These findings suggest a monoclonal origin of both glandular and hepatoid elements of HACS and support "HACS transdifferentiation" as the most accepted histogenesis.…”