title: Nuclear profiles of cancer cells reveal the metastatic potential of gastric cancer.
abstract: Nuclear profiles have been reported as useful prognostic predictors in various cancers. Data from computerized morphometry are objective and can be quickly derived using conventional microscopic analysis, but image analysis of nuclear features has only rarely been applied to investigations of gastric cancer. The aim of this study was to evaluate the correlation between one of these morphological nuclear features and the clinicopathological parameters in patients with gastric cancer. The morphometric nuclear feature (nuclear area) was analysed in 400 patients with gastric cancer. In each case, 300 cancer nuclei on routine haematoxylin and eosin-stained slides were analysed through the use of a computer-assisted image analysis system which traced the nuclear profiles (magnificationx400) on a computer monitor. The morphometric data were compared with the patients' clinicopathological status and survival rate. The mean nuclear area (NA) of cancer cells from 400 cases of gastric cancer was 47.2 microm(2). The NAs of cancer cells from tumours with microvessel invasion (lymphatic or venous invasion), lymph node metastasis or hepatic metastasis at the time of operation were significantly larger than those of cancer cells from tumours without such invasion or metastases. Cytokeratin (CK) immunostaining was performed on 2577 lymph nodes from 91 patients with advanced gastric cancer (pT3, pN0, pM0, stage II) to detect micrometastases. CK-positive lymph nodes were detected in 350 of 2577 lymph nodes (13. 6%) and in 62 of 91 patients (68.1%). The mean NA of cancer cells from 62 tumours with micrometastases (44 microm(2)) was larger than that of cancer cells from 29 tumours without micrometastases (38.8 microm(2), p=0.043), and a significant positive correlation was detected between the NAs of cancer cells from 91 tumours and the number of micrometastatic lymph nodes of 91 patients (rho=0.278, p=0. 008). Cancer cells with large NA correlated strongly with haematogenous and lymph node recurrence or relapse after gastrectomy and the NA of cancer cells was identified as an independent prognostic factor in gastric cancer. Nuclear morphometry is an objective, reproducible, and technically uncomplicated procedure. The NA of cancer cells correlates closely with the metastatic potential of gastric cancer. Nuclear morphometry may therefore be useful for the selection of patients who are at risk of haematogenous or lymph node metastatic recurrence after surgery.
authors.affiliation: Department of Surgery I, Faculty of Medicine, Tottori University, Nishicho 36-1. Yonago 683-8504, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ikeguchi
authors.forename: J
authors.initials: J
authors.lastname: Cai
authors.forename: S
authors.initials: S
authors.lastname: Oka
authors.forename: Y
authors.initials: Y
authors.lastname: Gomyou
authors.forename: S
authors.initials: S
authors.lastname: Tsujitani
authors.forename: M
authors.initials: M
authors.lastname: Maeta
authors.forename: N
authors.initials: N
authors.lastname: Kaibara
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary* / Q000648:ultrastructure*; D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007620:Karyometry / Q000379:methods; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000473:pathology / Q000648:ultrastructure*; D015996:Survival Rate