Atsunori Nitta

Proliferating Cell Nuclear Antigen Labeling Index of Preoperative Biopsy Specimens in Gastric Carcinoma with Special Reference to Prognosis

Background. Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase δ and is considered to correlate with the cells proliferative state. Immunohistochemical methods with a anti‐PCNA antibody (PC10) have particular advantages compared with other techniques because of the maintenance of the tissue architecture and simplicity of the methodology.

Association of tumor cell proliferation with lymph node metastasis in early gastric cancer.

Recently, many studies have reported on the relationship between malignant potential of neoplasms and cell proliferation. Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta and is considered to correlate with the cells proliferative state. In this study, we investigated the correlation between tumor cell proliferation and nodal status of early gastric carcinoma. One hundred two endoscopically biopsied specimens from patients with early gastric carcinoma prior to operation were investigated by an immunohistochemical study, using anti-PCNA monoclonal antibody. Correlation of PCNA labeling index (percentage of positive cells per over 500 tumor cells) with nodal status were studied. PCNA labeling index in patients with lymph node metastasis was significantly higher in those without metastasis. Moreover, multivariate analysis indicated that PCNA labeling index is an independent significant factor for lymph node metastasis. As a result of this study, PCNA labeling index was suggested to be effective as one of the predictors of lymph node metastasis.

Establishment of a cisplatin-resistant gastric carcinoma cell line OCUM-2M/DDP

Abstract A cis-diamminedichloroplatinum (CDDP)-resistant scirrhous gastric cancer cell line, OCUM-2M/DDP, was established by chronic exposure of cells of the parent scirrhous gastric cancer cell line, OCUM-2M, to CDDP at progressively increasing concentrations. The OCUM-2M/DDP cell line had an 11.3-fold higher level of resistance relative to its parent cell line as determined by a succinate dehydrogenase inhibition test. The biological and biochemical characteristics of the resistant and parent cell line were compared. There were differences in the modal chromosome number and DNA index, suggesting that some alterations of the DNA in the CDDP-resistant cells had occurred. Neither the parent nor resistant cell line expressed mdr-1 mRNA. After exposure to CDDP for 4 h, the intracellular platinum content of OCUM-2M cells was significantly higher than that of OCUM-2M/DDP cells (51.9±1.8 vs 16.4 plus 1.0 ng/mg protein, mean±SD, respectively). The GSH levels in OCUM-2M cells and OCUM-2M/DDP cells were 3.5±1.0 μg/mg protein and 16.8±1.2 μg/mg protein, respectively. These levels were also significantly different. These findings suggest that the possible mechanisms of resistance to CDDP in OCUM-2M/DDP cells may be a decrease in intracellular CDDP accumulation and detoxication by GSH. This OCUM-2M/DDP cell line could be used in further investigations of the mechanism of CDDP resistance in gastric cancer.

Immunohistochemical Study of PCNA (Proliferating Cell Nuclear Antigen) in Gastric Cancer with Special Reference to Progression and Prognosis

We investigated the correlation between tumor’s proliferative activity and progression of gastric carcinoma using immunohistochemical staining with PC10 monoclonal antibody recognizing Proliferating Cell Nuclear Antigen (PCNA). PCNA labeling index became higher as the histologic stage increased. Also, in patients with lymph node metastasis and peritoneal metastasis, labeling index was significantly higher. Moreover in patients with high PCNA labeling index (≧50%), prognosis was significantly poorer than in those with low index (<50%). These result suggested PCNA labeling index is associated with tumor stage and is useful as one of the prognostic factors.