The role of histological investigation in prognostic evaluation of advanced gastric cancer - Analysis of histological structure and molecular changescompared with invasive pattern and stage

The relative contribution of tumour histology or molecular changes, compare d with invasion pattern or stage, to prognostic assessment of gastric cance r was investigated in a series of 185 advanced (T2 to T4, stage IB to IV) c ancers that had undergone intentionally curative surgery at Varese General Hospital. Survival analysis of the histological types considered in commonl y used classifications, such as Lauren, Kubo, the World Health Organization (WHO) and related classifications, allowed separation of a small high-grad e (Hg, 12 cases) group of adenosquamous, anaplastic and small cell endocrin e carcinomas from a large cohesive group (C, 86 glandular or solid cancers) and from another large (87 cases) group of tumours with dissociated cells [29 diffuse (D) and 58 mixed (M) tumours]. Univariate and multivariate anal ysis showed the independent prognostic value of this C/M+D/Hg classificatio n approach, which proved superior to other classifications and to cell diss ociation at the growing front or angio, lympho and neuro-invasion. Expressi on of sialyl Lewis(c), the DUPAN-2 antigen, proved to be an independent pre dictor of worse survival among tumours beyond stage I, showing an exclusive ly or predominantly cohesive structure. Microsatellite instability (MSI) pr edicted favourable survival in purely cohesive tumours of intermediate (II) stage, especially of solid/medullary and lymphoid stroma/lympho-epitheliom a-like structure, among which two distinct tumour subsets were characterise d, one MSI-positive and the other Epstein-Barr virus positive. T2N0M0 (stag e IB) tumours showed mostly favourable survival independently from histolog ical type, invasive pattern, DUPAN-2 or MSI status. It is concluded that an appropriate histological evaluation, coupled with sialylated glycoproteins histochemistry and, for stage-H tumours, MSI tests may contribute signific antly to prognostic assessment of tumours beyond stage I. However, the stag e itself, with special reference to lymph-node metastases and invasion leve l beyond subserosa, remains the most important prognostic clue for gastric cancer.