Four resections for hepatic metastasis from gastric cancer: histochemical analysis of cell proliferation, apoptosis, and angiogenesis

In a patient with gastric cancer (GC) associated with one synchronous and three metachronous hepatic metastases (HM), who underwent four hepatectomies, we carried out histochemical investigations regarding cell proliferation, apoptosis, and angiogenesis in the GC and HM. Tissue samples were taken from the primary GC and four HM. Ki-67 immunostaining was performed to evaluate cell proliferation and determine the labeling index (Ki-67 LI; ie, the percentage of cancer cells with nuclei stained for Ki-67). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) was performed to evaluate apoptosis and determine the apoptotic index (ie, the percentage of TUNEL-positive cells), and immunostaining for factor VIII-related antigen was performed to evaluate angiogenesis and measure microvessel density (MVD). The Ki-67 LI was 43.2% in the primary GC and 39.9% in the synchronous HM, and the LI increased with the number of resections of metachronous HM. The apoptotic index was 3.36% in the primary GC, and 5.30% in the synchronous HM, and the index decreased after further resections of the metachronous HM. The MVD was 35 in the primary GC, and 22 in the synchronous HM, and it increased with the number of resections of metachronous HM. The primary GC in this patient may have strongly influenced the growth of HM through effects on cell proliferation, apoptosis, and angiogenesis.