Expression of biomarkers modulating prostate cancer angiogenesis: differential expression of annexin II in prostate carcinomas from India and USA.
Expression of biomarkers modulating prostate cancer angiogenesis: differential expression of annexin II in prostate carcinomas from India and USA.
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DOI：
10.1186/1476-4598-2-34
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发表时间：
2003-10-08
期刊：
影响因子：
37.3
通讯作者：
Vishwanatha, Jamboor K
中科院分区：
文献类型：
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作者：
Banerjee, Abhijit G;Liu, Jie;Vishwanatha, Jamboor K
背景：前列腺癌（PCa）的发病率与患者的遗传、地理和种族饮食背景有关，而血管生成是通过生物大分子的肿瘤-基质相互作用的精细相互作用来调节的。我们假设，在两个不同的人群中，对四种生物标志物在前列腺癌进展中调节血管生成的综合分析可能解释发病率的差异。结果：42例PCa活检的免疫组织化学分析显示，尽管在Gleason评分（GS）在6到10之间的印度和美国人群中ax - ii表达缺失，但在美国的整个高分级（GS bbbb8） PD PCa样本中，高达25%的细胞显示出强烈的ax - ii局灶性膜染色，这与来自印度的类似分级标本不同。与此观察结果一致的是，前列腺癌细胞PC-3、DU-145和MDA PCa 2A，而LNCaP-R、LNCAP-UR和MDA PCa 2B细胞系不表达anxi - ii。用Aza-dC转录再激活Anx-II基因不能完全解释原发性PCa中Anx-II蛋白的丢失。环氧化酶-2 （COX-2）在大多数高分级PIN和部分MD PCa及周围基质中均有中等表达。COX-2在PD PCa中不表达（GS约为7-10），而邻近的平滑肌细胞染色弱阳性。Decorin的表达仅在高级别PIN中观察到，而在任何前列腺癌、萎缩或BPH中均未观察到，而BPH间质区域的DCN染色强烈，并且随着PCa的进展而减少。在大多数MD PCa中表达弱，在所有BPH中表达中等，在PD PC中表达中度，在PIN、萎缩和邻近间质中表达弱。结论：促血管生成和抗血管生成调节剂的表达随前列腺癌分期而变化，但与血管生成状态相关。在高级别PCa标本中，仅在US中出现了局灶性膜染色，表明ax - ii的差异表达。与印第安标本相比，美洲标本的COX-2染色更强。在印度和美国的标本中，DCN和VCN在进展阶段的顺序表达相似，表明没有基于人群的差异。ax - ii在前列腺癌进展中的机制和调控作用有待进一步研究。
BACKGROUND: Prostate cancer (PCa) incidences vary with genetic, geographical and ethnic dietary background of patients while angiogenesis is modulated through exquisite interplay of tumor-stromal interactions of biological macromolecules. We hypothesized that comprehensive analysis of four biomarkers modulating angiogenesis in PCa progression in two diverse populations might explain the variance in the incidence rates.RESULTS: Immunohistochemical analysis of 42 PCa biopsies reveals that though Anx-II expression is lost in both the Indian and American population with Gleason scores (GS) ranging between 6 and 10, up to 25 % of cells in the entire high grade (GS > 8) PD PCa samples from US show intense focal membrane staining for Anx-II unlike similarly graded specimens from India. Consistent with this observation, the prostate cancer cell lines PC-3, DU-145 and MDA PCa 2A, but not LNCaP-R, LNCAP-UR or MDA PCa 2B cell lines, express Anx-II. Transcriptional reactivation of Anx-II gene with Aza-dC could not entirely account for loss of Anx-II protein in primary PCa. Cyclooxygenase-2 (COX-2) was moderately expressed in most of high grade PIN and some MD PCa and surrounding stroma. COX-2 was not expressed in PD PCa (GS approximately 7-10), while adjacent smooth muscles cells stained weakly positive. Decorin expression was observed only in high grade PIN but not in any of the prostate cancers, atrophy or BPH while stromal areas of BPH stained intensively for DCN and decreased with advancing stages of PCa. Versican expression was weak in most of the MD PCa, moderate in all of BPH, moderately focal in PD PC, weak and focal in PIN, atrophy and adjacent stroma.CONCLUSIONS: Expression of pro- and anti-angiogenic modulators changes with stage of PCa but correlates with angiogenic status. Focal membrane staining of Anx-II reappears in high grade PCa specimens only from US indicating differential expression of Anx-II. COX-2 stained stronger in American specimens compared to Indian specimens. The sequential expression of DCN and VCN in progressive stages was similar in specimens from India and USA indicating no population-based differences. The mechanistic and regulatory role of Anx-II in PCa progression warrants further investigation.