| Bronchioloalveolar carcinoma(BAC) is a particular subtype of pulmanary adenocarcinoma,which derives from clara cell and type II pneumocyte. The incidence of BAC appears to be rising recently. The etiology and pathogenesis of this unique neoplastic disease are still unclear, many studies of oncogene and tumor suppressor gene expression include BAC with all adenocarcinoma or non-small cell lung cancer, rather than as a separate category.Recent studies have revealed that uncontrolled cell cycle is very important to uncontrolled cell proliferation and carcinogenesis. Cyclin-dependent kinase (CDK), together with cyclin and CDK inhibitor, govern cell cycle progression in eukaryotic cell. In cell cycle, different phase is regulated by different factors, in them, Grphase regulators are most closely related to carcinogenesis. Proto-oncogene cyclin Dl encodes cyclin Dl protein, which acts as an important positive regulator in G1/S transition, and appears to be closely linked with carcinogenesis, the overexpression of cyclin Dl has been reported in a variety of malignant tumors. p27 is an important CDK inhibitor, which binds to and inhibits preferentially G1-phase kinases thereby arresting the cell cycle at G1-phase. Decreased p27 expression has been shown to associated with the development and malignant progression in many human malignant tumors, andprovides independent prognostic information. To our knowledge, p27 expression in BAC has not previously been reported in the literature, cyclin Dl expression in BAC not reported except for 19 cases in the study of McDonald et al. Ki-67 antigen is a cell cycle-related nuclear antigen, anti-Ki67 antibody is widely used for detecting proliferating cells. The relationship between Ki-67 expression and clinicopathological parameters is different in different tumors. Here we evaluated the expression of the cell cycle-related proteins cyclin Dl, p27 and Ki-67 in 43 surgically resected BACs using immunohistochemical En Vision method, discussed the relationship between the expression of the genes and their clinicopathological significances.Materials and Methods43 cases BACs and 13 paracancerous normal pulmonary tissue were taken from the surgically resected specimen in Sir Run Run Shaw Hospital from 1994 to 2000. Histological subtyping of BAC according to WHO(1999) criteria revealed that 39 were nonmucinous, 4 were mucinous. According to the international TNM staging system, 19 patients were classfied at stage I, 12 at stage II, 6 at stage III, 6 at stage IV. Expression of cyclin Dl, p27 and Ki-67 was detected by immunohistochemical En Vision method, with 1:50 dilution of primary antibody of cyclin Dl, p27 and Ki-67, positive and negative controls were designed. Judging and grading system: for each antibody, positive immunostaining appears as yellow brown nucleus with clear background, the immunohistochemical stains were graded on a semiquantitative scale according to the prevalence of nuclear staining and combined with staining color intensity: <5% positive cells (-), 5%~25%(+), 25%~50%(++), >50%(+++). Statistical analysis: chi-square test and Fisher' s exact test.Results and DiscussionCyclin Dl expression was seen in 28/43 BACS(65. 1%), while no expression was observed in matched pulmonary tissue, the difference wasvery significant(Fisher's exact test, p<0.01). This result indicates that cyclin Dl overexpression plays an important role in the development of BAC. In the group with lymph node metastasis, the primary tumor and metastatic tumor showed the same positivity. No statistically significant association was found between cyclin Dl expression data and sex, age, tobacco use history, subtype of BAC(mucinous vs. nonmucinous), lymph node status and clinical stage, but the cyclin Dl expression was negatively correlated with tumor size, the positivity in <3cm group was significantly higher than in >3cm group (Fisher' s exact test, p<0. 05), this finding is not in agreement with literature observations. We think this result may be caused by the following rea... |
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