STOMACH

PDX1 homeobox protein expression in pseudopyloric glands and gastric carcinomas

H Sakai¹, Y Eishi², X-L Li¹, Y Akiyama¹, S Miyake¹, T Takizawa³, N Konishi⁴, M Tatematsu⁵, M Koike², Y Yuasa¹

¹ Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan
² Department of Human Pathology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan
³ Department of Surgical Pathology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan
⁴ Department of Pathology, Nara Medical University, Nara, Japan
⁵ Laboratory of Pathology, Aichi Cancer Centre Research Institute, Nagoya, Japan

Correspondence to:
Correspondence to:
Professor Y Yuasa
Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; yuasa.monc{at}tmd.ac.jp

Background and aims: Although it has been reported that intestinal metaplasia implicated in gastric carcinogenesis is induced by the ParaHox gene CDX2, it is unclear which genes are responsible for the formation of pseudopyloric glands and whether they play a role in gastric carcinogenesis. Pancreatic-duodenal homeobox 1 (PDX1) is also a ParaHox gene which contributes to the genesis and development of the pancreas, duodenum, and antrum. To clarify its significance for the formation of pseudopyloric glands and gastric carcinogenesis, we investigated expression of PDX1 and mucin in gastric carcinomas and surrounding mucosa.

Methods: Gastric carcinoma tissues from 95 patients were used for immunohistochemical analyses of PDX1, and mucins MUC6 and MUC5AC.

Results: PDX1 was found to be frequently expressed in pseudopyloric glands and intestinal metaplasia. MUC6 was more abundant than MUC5AC in pseudopyloric glands while higher levels of MUC5AC than MUC6 were evident in intestinal metaplasia. The frequency of PDX1 positive reactivity was higher in differentiated type carcinomas (39/43, 90.7%) and T1 carcinomas (42/43, 97.7%) than in undifferentiated type (33/52, 63.5%) and T2–4 (30/52, 57.7%) carcinomas. PDX1 and MUC6 double positive expression was observed in carcinomas, respectively, including the corpus, and also correlated with histological type and depth of invasion. In contrast, no link was apparent between PDX1 and MUC5AC double positive reactivity and histological type.

Conclusion: Our study suggests that PDX1 plays an important role in the development of pseudopyloric glands, and that pseudopyloric glands may reflect a condition associated with gastric carcinogenesis.

Keywords: PDX1; pseudopyloric gland; gastric carcinoma; mucin expression; immunohistochemistry

Abbreviations: PDX1, pancreatic-duodenal homeobox 1; MUC6, MUC5AC, mucins MUC6 and MUC5AC; PCR, polymerase chain reaction; GST, glutathione-S-transferase; GST-PDX1, glutathione-S-transferase-PDX1 fusion protein; PBS, phosphate buffered saline; PBST, PBS and 0.05% Tween 20

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