Two molecular pathways to transitional cell carcinoma of the bladder.
Two molecular pathways to transitional cell carcinoma of the bladder.
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发表时间：
1994-02
期刊：
影响因子：
11.2
通讯作者：
C. Spruck;P. F. Ohneseit;M. Gonzalez‐Zulueta;D. Esrig;N. Miyao;Y. Tsai;S. Lerner;C. Schmutte;A. Yang;R. Cote;L. Dubeau;P. Nichols;G. Hermann;K. Steven;T. Horn;D. Skinner;P. Jones
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作者：
C. Spruck;P. F. Ohneseit;M. Gonzalez‐Zulueta;D. Esrig;N. Miyao;Y. Tsai;S. Lerner;C. Schmutte;A. Yang;R. Cote;L. Dubeau;P. Nichols;G. Hermann;K. Steven;T. Horn;D. Skinner;P. Jones
非侵袭性膀胱移行细胞癌可以有两种不同的形态，这表明它们包含不同的基因改变。乳头状移行细胞癌(T(A)瘤)通常是多灶性的，只是偶尔进展，而扁平肿瘤(原位癌，CIS)，通常进展为侵袭性疾病。我们检查了216个不同阶段的膀胱肿瘤和组织病理学，以检测两种先前被描述为对膀胱肿瘤发生有重要影响的基因改变。在70例T(A)肿瘤中，24例(34%)存在9号染色体杂合性缺失，而在24例CIS和异型增生病变中仅3例(12%)存在9号染色体杂合性缺失(P=0.04)。相比之下，36例T(A)肿瘤中只有1例(3%)含有p53基因突变，而23例CIS和异型增生中有15例(65%)(P<；0.001)，这一频率与肌肉浸润性肿瘤(25/49；51%)相当。独联体和异型增生中P53突变的存在可以解释它们进展的倾向，因为这些突变已知会破坏基因组的稳定。对几对涉及CIS和浸润性癌的肿瘤的分析提供了证据，表明在某些情况下，9号染色体的改变可能涉及CIS向更具侵袭性的肿瘤的进展，以及它在T(A)肿瘤的起始中的作用。然而，在一些患者中，CIS和继发性肿瘤被发现包含不同的基因变化，这表明了不同的进展途径。因此，膀胱癌的发生可能通过两种不同的基因改变途径进行，从而导致不同形态和病理的浅表肿瘤的发生。
Noninvasive transitional cell carcinomas of the bladder can have two distinct morphologies suggesting they contain different genetic alterations. Papillary transitional cell carcinomas (T(a) tumors) are often multifocal and only occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently progress to invasive disease. We examined 216 bladder tumors of various stages and histopathologies for two genetic alterations previously described to be of importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was observed in 24 of 70 (34%) T(a) tumors but was present in only 3 of 24 (12%) CIS and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3%) T(a) tumors contained a p53 gene mutation compared to 15 of 23 (65%) CIS and dysplasias (P < 0.001), a frequency comparable to that observed in muscle invasive tumors (25 of 49; 51%). The presence of p53 mutations in CIS and dysplasia could explain their propensities to progress since these mutations are known to destabilize the genome. Analysis of several tumor pairs involving a CIS and an invasive cancer provided evidence that the chromosome 9 alteration may in some cases be involved in the progression of CIS to more invasive tumors, in addition to its role in the initiation of T(a) tumors. However, the CIS and secondary tumor were found to contain different genetic alterations in some patients suggesting divergent progression pathways. Bladder carcinogenesis may therefore proceed through two distinct genetic alteration pathways responsible for generating superficial tumors with differing morphologies and pathologies.