Abstract
Prognosis of gastric cancer is dramatically improved by early diagnosis. Correa’s cascade correlates the expression of some molecular markers with the progression of preneoplastic lesions toward carcinoma. This article reviews the diagnostic and prognostic values of molecular markers in complete (MUC2) and incomplete (MUC2, MUC5AC, and MUC6) intestinal metaplasia, gastric dysplasia/intra-epithelial neoplasia, and early gastric cancer. In particular, considering preinvasive neoplasia and early gastric cancer, some studies have demonstrated a correlation between molecular alterations and prognosis, for example, mucins phenotype in gastric dysplasia, and GATA6, TP53 mutation/LOH and MUC6 in early gastric cancer. Moreover, this review considers novelties from the literature regarding the (immuno)histochemical characterization of diffuse-type/signet ring cell gastric cancer, with particular attention to clinical outcomes of patients. The aim of this review is the evaluation of the state of the art regarding suitable biomarkers used in the pre-surgical phase, which can distinguish patients with different prognoses and help decide the best therapeutic strategy.
Highlights
Worldwide, gastric cancer ranks fifth in incidence and fourth in mortality, registering one million new cases and an estimated 769,000 deaths in 2020 [1]
Mucins are glycoproteins of gastric mucus that protect gastric mucosa and are normally expressed in non-neoplastic gastric tissue [20]. Their overexpression and decrease in the immune response are associated with neoplastic transformation. Their levels correlate with the histological origin of the tumor (e.g., MUC5AC is secreted by antrum and body foveolar cells, and MUC6 by pyloric glands) [21]
CDX1 transgenic mouse model showed that the replacement of gastric mucosa with Intestinal metaplasia (IM) involves all four epithelial cell types, whereas only pseudopyloric gland metaplasia was observed in the CDX2 transgenic mouse
Summary
Gastric cancer ranks fifth in incidence and fourth in mortality, registering one million new cases and an estimated 769,000 deaths in 2020 [1]. Incidence and mortality rates of non-cardia cancer have been decreasing over the last fifty years due to prevention (e.g., Helicobacter pylori infection and storage of foods), a significant increase in the incidence of stomach cancer among young adults (aged < 50 years) was reported [2] Both gastric precancerous lesions and gastric cancer are associated with a spectrum of genetic and epigenetic abnormalities [3,4,5]. The precancerous stages of intestinal-type gastric cancer represent a complex process, part of which results in a transformation of the normal mucosa to an intestinal metaplastic mucosa through a series of lesions forming a continuum This sequence of events may last for several years and is designated as Correa’s cascade of multistep gastric carcinogenesis [16]. Outcomes and mucins expression seem to differ between Caucasian and Asian patients
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