Häggman M J, Wojno K J, Pearsall C P, Macoska J A
Department of Surgery, The Michigan Prostate Institute, The University of Michigan Medical Center, Ann Arbor 48109-0680, USA.
Urology. 1997 Oct;50(4):643-7. doi: 10.1016/S0090-4295(97)00304-X.
Previous work has suggested that prostatic intraepithelial neoplasia (PIN) may be a premalignant lesion important in tumorigenesis of the prostate. However, to adequately test this hypothesis at the genetic level, it is necessary to determine whether lesions in close proximity demonstrate similar genetic alterations and, hence, whether an "evolutionary" relationship might exist between PIN and tumor in the same prostate. Therefore, the purpose of this study was to examine at least two PIN lesions per prostate (one adjacent to and another distant from malignant lesions in the same prostate) for similarities or differences in the types and frequencies of genetic alterations.
To accomplish this goal, DNA was extracted from microdissected PIN, tumor, and normal epithelial tissue samples from 48 radical prostatectomies and amplified using polymerase chain reaction techniques at highly polymorphic microsatellite repeat sequences at proximal (D8S87, 8p12) and distal (NEFL, 8p21) loci on the short arm of chromosome 8. PIN specimens were either adjacent to (within one high-power microscopic field [HPF]) or distant from (separated by two or more HPFs) tumor specimens from the same patients.
Similar fractional allelic loss frequencies were observed for informative tumor (10 [35%] of 29) and PIN (6 [21%] of 29) samples at the NEFL locus, but allelic loss at the D8S87 locus was observed only in tumors (8 [22%] of 36 informative samples). Moreover, allelic loss at the NEFL locus involved the same allele in 4 cases and different alleles in 3 cases. Interestingly, all 4 cases with the same allele loss were from adjacent PIN and tumor tissues, and all 3 with different allele loss were from distant PIN and tumor.
These results suggest that PIN and invasive cancer share common genetic events (eg, deletion at the NEFL locus) along the same pathway of development in the prostrate.
先前的研究表明，前列腺上皮内瘤变（PIN）可能是前列腺肿瘤发生过程中一种重要的癌前病变。然而，要在基因水平充分验证这一假说，有必要确定紧邻的病变是否表现出相似的基因改变，进而确定同一前列腺内的PIN与肿瘤之间是否可能存在“进化”关系。因此，本研究的目的是检查每个前列腺至少两个PIN病变（一个紧邻同一前列腺内的恶性病变，另一个与之相距较远），以观察基因改变的类型和频率的异同。
为实现这一目标，从48例根治性前列腺切除术中的显微切割PIN、肿瘤和正常上皮组织样本中提取DNA，并使用聚合酶链反应技术在8号染色体短臂近端（D8S87，8p12）和远端（NEFL，8p21）位点的高度多态微卫星重复序列处进行扩增。PIN标本与同一患者的肿瘤标本相邻（在一个高倍显微镜视野[HPF]内）或相距较远（相隔两个或更多HPF）。
在NEFL位点，信息丰富的肿瘤样本（29例中的10例[35%]）和PIN样本（29例中的6例[21%]）观察到相似的等位基因缺失频率，但仅在肿瘤中观察到D8S87位点的等位基因缺失（36例信息丰富的样本中的8例[22%]）。此外，NEFL位点的等位基因缺失在4例中涉及相同等位基因，在3例中涉及不同等位基因。有趣的是，所有4例相同等位基因缺失的病例均来自相邻的PIN和肿瘤组织，而所有3例不同等位基因缺失的病例均来自相距较远的PIN和肿瘤。
这些结果表明，PIN和浸润性癌在前列腺的同一发育途径中存在共同的基因事件（如NEFL位点的缺失）。
