Clinicopathologic and immunohistochemical characteristics of gastric adenocarcinoma with enteroblastic differentiation: a study of 29 cases.

Abstract

BACKGROUND:

Gastric adenocarcinoma with enteroblastic differentiation (GAED) has been recognized as a variant of alpha-fetoprotein (AFP)-producing gastric carcinoma, although its clinicopathologic and immunohistochemical features have not been fully elucidated.

METHODS:

To elucidate the clinicopathologic and immunohistochemical features of GAED, we analyzed 29 cases of GAED, including ten early and 19 advanced lesions, and compared these cases with 100 cases of conventional gastric adenocarcinoma (CGA). Immunohistochemistry for AFP, glypican 3, SALL4, and p53 was performed, and the phenotypic expression of the tumors was evaluated by immunostaining with antibodies against MUC5AC, MUC6, MUC2, CD10, and caudal-type homeobox 2 (CDX2).

RESULTS:

Lymphatic and venous invasion was more frequent in GAED (76 and 72 %) than in CGA (41 and 31 %; P ≤ 0.001). Lymph node metastasis was more frequently observed in GAED (69 %) than in CGA (38 %; P = 0.005), as were synchronous or metachronous liver metastases (GAED, 31 %; CGA, 6 %; P ≤ 0.001). Immunohistochemically, all GAED were positive for at least one of three enteroblastic linage markers (AFP, glypican 3, and SALL4). Glypican 3 was the most sensitive marker (83 %) for GAED, followed by SALL4 (72 %) and AFP (45 %), whereas no CGA was positive. Furthermore, the rate of positive p53 staining was 59 % in GAED. Regarding the mucin phenotype, CD10 and CDX2 were diffusely or focally expressed in all GAED cases. Invasive areas with hepatoid or enteroblastic differentiation were negative for CD10 and CDX2.

CONCLUSIONS:

Clinicopathologic features of GAED differ from those of CGA. GAED shows aggressive biological behavior, and is characteristically immunoreactive to AFP, glypican 3, or SALL4.

• Authors: Takashi Murakami, Takashi Yao, Hiroyuki Mitomi, Takashi Morimoto, Hiroya Ueyama, Kenshi Matsumoto, Tsuyoshi Saito, Taro Osada, Akihito Nagahara, Sumio Watanabe
• Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (Gastric Cancer) Vol. 19 Issue 2 Pg. 498-507 (Apr 2016) ISSN: 1436-3305 [Electronic] Japan
• PMID: 25893262 (Publication Type: Journal Article)

Chemical References

• AFP protein, human
• Biomarkers, Tumor
• CDX2 Transcription Factor
• CDX2 protein, human
• GPC3 protein, human
• Glypicans
• MUC5AC protein, human
• MUC6 protein, human
• Mucin 5AC
• Mucin-6
• SALL4 protein, human
• TP53 protein, human
• Transcription Factors
• Tumor Suppressor Protein p53
• alpha-Fetoproteins

Topics

• Adenocarcinoma (immunology, mortality, pathology)
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (immunology, metabolism)
• CDX2 Transcription Factor (immunology, metabolism)
• Female
• Follow-Up Studies
• Glypicans (immunology, metabolism)
• Humans
• Immunohistochemistry
• Liver Neoplasms (pathology, secondary)
• Lymph Nodes (pathology)
• Lymphatic Metastasis (pathology)
• Male
• Middle Aged
• Mucin 5AC (immunology, metabolism)
• Mucin-6 (immunology, metabolism)
• Stomach Neoplasms (immunology, mortality, pathology)
• Transcription Factors (immunology, metabolism)
• Tumor Suppressor Protein p53 (immunology, metabolism)
• alpha-Fetoproteins (immunology, metabolism)