Malignant transformation of hyperplastic gastric polyps: An immunohistochemical and pathological study of the changes of neoplastic phenotype

Abstract

In spite of the evidence that the malignant transformation of gastric hyperplastic polyps (HPs) is a rare event, it must always be taken into account during diagnosis. The aim of the current study was to clarify the mechanism of the malignant transformation of gastric hyperplasia polyps, with focus on phenotypic expression, cell proliferation and p53 overexpression. Immunohistochemistry for mucin phenotypic markers, including MUC1, MUC2, MUC5AC, MUC6, tight junction factors (claudin-3, -4 and -18), an intestinal phenotypic marker [caudal type homeobox 2 (Cdx2)], Ki-67 proliferative index and p53 overexpression, was performed on archival specimens of gastric polyps excised from six patients. Histologically, the intermingled components of several lesions were present in these polyps. Furthermore, the cancer components were predominantly differentiated adenocarcinoma. Immunohistochemically, all hyperplastic components expressed MUC5AC, but did not exhibit positivity for MUC2. Additionally, the majority of hyperplastic components were immunonegative for claudin-3, while claudin-3 positivity was observed in the majority of areas of dysplasia and carcinoma. Expression of claudin-4 was also observed in the majority of cases and claudin-18 was preserved in the hyperplastic, dysplastic and adenocarcinomatous lesions of all cases. Nuclear accumulation of Cdx2 was detected in almost all the samples with dysplasia and carcinoma, while nuclear p53 was detected in 24–80% of the dysplastic areas and >85% of the cancer components. The Ki-67 labeling index appeared to correlate with neoplastic progression. The observations provided evidence that the mechanism underlying malignant transformation of gastric HPs may occur by multistep carcinogenesis, such as the hyperplasia-adenoma (dysplasia)-adenocarcinoma sequence, and these neoplastic cells may acquire various phenotypes during this process.

Pathophysiological and clinical aspects of gastric hyperplastic polyps

“…It is estimated that most of GHPs remain stable in time, but 27% may enlarge[15]. It appears that, in addition to age, there are known some clinical factors predicting for the possibility of neoplastic transformation of GHPs, such as polyp size (greater than 1 cm), pedunculated morphology, postgastectomy state, and synchronous neoplastic lesion[16,17]. …”

“…The research seems to confirm the theory of neoplastic transformation in hyperplastic polyps of the hyperplasia-dysplasia-adenocarcinoma type. The expression of certain membrane proteins called claudins (Cld) that are found in tight intracellular junctions and are responsible for cell membrane integrity is one of the markers of malignant transformation within hyperplastic polyps of the stomach, since the expression of Cld-3 has been demonstrated only within the foci of intraepithelial neoplasia and cancer[16]. …”

Gastric hyperplastic polyps coexisting with early gastric cancers, adenoma and neuroendocrine cell hyperplasia

“…It is well known that gastric cancer is more likely to develop in a stomach containing hyperplastic polyps [7,17,18,19,20,21]. Most GHP were found in the gastric mucosa with a precancerous condition: chronic gastritis -mainly H. pylori chronic gastritis [22].…”

“…The malignant transformation of GHP significantly correlates with the size > 1 cm, pedunculated shape, post-gastrectomy state and synchronous neoplastic lesions [7]. Therefore, endoscopic polypectomy should be considered in these GHP to avoid the risk of missing neoplastic potential [7].…”

Gastric adenocarcinoma arising in giant hyperplastic polyp

“…Сообщается, что большинство ГП остаются стабильными с течением времени и только 27% могут увеличиваться в размере [16]. Предполагается, что признаками высокого риска злокачественной трансформации ГП, помимо возраста, могут служить следующие клинические факторы: размер полипа (более 1 см), наличие у него ножки, состояние после гастрэктомии и наличие синхронной злокачественной опухоли в желудке [17,18]. Частота встречаемости рака в ГП напрямую зависит от размера полипа [19].…”