Histologic Grade and Cellular Proliferation at the Deepest Invasive Portion Correlate with the High Malignancy of Submucosal Invasive Gastric Carcinoma

Abstract

To establish appropriate indications for endoscopic treatment of submucosal invasive gastric carcinoma, we investigated clinicopathologic features and proliferating cell nuclear antigen (PCNA) expression at the deepest invasive portion of 192 differentiated submucosal invasive gastric carcinomas that had been surgically resected. Lymph node metastasis was demonstrated in 30 (15.6%) of 192 lesions. Histologic heterogeneity (based on differentiation at the deepest invasive portion) was demonstrated in 36 (18.8%) of the 192 lesions. In 159 lesions, excluding 33 undifferentiated lesions at the deepest invasive portion, the depth of invasion, histologic grade, lymph vessel involvement, infiltrative growth pattern (INF) and existence of an ulceration were all significantly correlated with the incidence of lymph node metastasis. The lesions with both well-differentiated adenocarcinoma (WELL) and minimal submucosal invasion (sml) showed no lymph node metastasis. PCNA expression was estimated in 59 good stained lesions. The mean PCNA labeling index (LI) was 50.9 ± 7.2% in lesions with lymph node metastasis and 43.7 ± 9.3% in those without lymph node metastasis (p < 0.05). In addition, PCNA-LI also correlated significantly with the histologic grade, depth of invasion, INF and lymph vessel involvement. These results indicate that the submucosal invasive gastric carcinoma with both WELL and sm 1, which shows no other risk factors, can be considered as the appropriate indication for curative endoscopic treatment. The PCNA-LI at the deepest invasive portion is useful in understanding the biology of lymph node metastasis in submucosal invasive gastric carcinoma.

Increased proliferative activity caused by loss of p21WAF1/CIP1 expression and its clinical significance in patients with early‐stage gastric carcinoma

“…[7][8][9][10][11][12] Previous studies showed that patients with early-stage gastric carcinoma who had lymph node metastases had a higher PCNA labeling index compared with patients who had no lymph node metastasis. 27,28 In the current study, we also found that patients with early-stage gastric carcinoma in the high labeling group had a significantly higher rate of lymph node metastasis compared with patients in the low labeling group. In the study by Isozaki et al, 29 the PCNA labeling index among 125 patients with gastric carcinoma was significantly higher in patients who had lymph node metastasis compared with patients who did not have lymph node metastasis.…”

Immunohistochemical Defection of Proliferating Cell Nuclear Antigen and p53 Expression in Carcinoma of the Extrahepatic Bile Duct

“…Previous reports have demonstrated that PCNA labeling rates are closely associ ated with the prognosis or the depth of tumor invasion in gastric cancers [17][18][19]. PCNA LI at the deepest invasive portion significantly correlated with the depth of invasion and lymph vessel involvement in gastric carcinomas [20]. These reports concur with our findings.…”

Clinical validity of endoscopic submucosal dissection for submucosal invasive gastric cancer: a single-center study

“…As we reported previously [30], when examining SM-GCs, it is important to take into account the histologic type of the deepest invasive portion in addition to the main histologic type. Hanaoka et al [31] reported that, in SM-GCs of mixed differentiated and undifferentiated types, the undifferentiated-type-predominant mixed-type showed a significantly higher incidence of lymph node metastasis with a significantly greater depth of submucosal invasion compared to the differentiated type.…”