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唾液腺癌中 PLAG1 和 HMGA2 重排的分析及前病变作用的研究。

An analysis of PLAG1 and HMGA2 rearrangements in salivary duct carcinoma and examination of the role of precursor lesions.

机构信息

Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.

出版信息

Histopathology. 2013 Aug;63(2):250-62. doi: 10.1111/his.12152. Epub 2013 Jun 6.

DOI:10.1111/his.12152
PMID:23738717
Abstract

AIMS

Salivary duct carcinoma (SDC) often arises in pleomorphic adenoma (PA). Putative precursors, including low-grade cribriform cystadenocarcinoma (LGCCC) and ductal carcinoma in-situ (DCIS), are more controversial. Rearrangement of PLAG1 or HMGA2 is seen in 50-70% of PAs, but this has not been investigated in SDC. Using a large collection of SDCs from a single institution, we aimed to study these genes by fluorescence in-situ hybridization (FISH), and to correlate the presence of precursor lesions/intraductal proliferations with gene alterations.

METHODS AND RESULTS

Forty-four SDCs were stained for smooth muscle actin, CK14, and p63, and examined with PLAG1 and HMGA2 FISH. Eight cases were SDC ex-PA; ten had a hyalinized nodule (HN), which is suspicious for PA; six arose in association with LGCCC; and twenty were 'de-novo' SDCs. Ten cases had PLAG1 rearrangement/amplification (22.7%) and eight had HMGA2 (18.2%) rearrangement/amplification. The positive cases were four SDC ex-PAs, eight SDCs with an HN, and five 'de-novo' SDCs. Twenty-three SDC ex-PAs were present in total (52.3%). All six SDC ex-LGCCCs were FISH-negative. Myoepithelial staining surrounded all LGCCCs, and demonstrated DCIS in 17 cases. Eleven DCIS lesions were in SDC ex-PAs or FISH-positive 'de-novo' SDCs. These cases represent 'cancerization' of ducts. Only six FISH-negative 'de-novo' SDCs showed DCIS.

CONCLUSIONS

A large proportion of SDCs arise in PAs (with or without residual evidence of a PA). A small proportion of SDCs arise in LGCCCs. Cases showing DCIS often represent cancerization.

摘要

目的

唾液腺癌(SDC)常起源于多形性腺瘤(PA)。有假说认为,低级别筛状囊腺癌(LGCCC)和导管原位癌(DCIS)为其潜在前体病变,但这一假说仍存在争议。PA 中约有 50-70%存在 PLAG1 或 HMGA2 的重排,但尚未在 SDC 中进行过研究。本研究通过荧光原位杂交(FISH)检测,对单一机构收集的大量 SDC 标本进行了这两种基因的研究,并将前体病变/导管内增生与基因改变相关联。

方法和结果

对 44 例 SDC 进行了平滑肌肌动蛋白、CK14 和 p63 染色,并进行了 PLAG1 和 HMGA2 FISH 检测。8 例为 SDC 源于 PA;10 例有透明样变性结节(HN),提示为 PA;6 例与 LGCCC 相关;20 例为“新发”SDC。10 例存在 PLAG1 重排/扩增(22.7%),8 例存在 HMGA2 重排/扩增(18.2%)。阳性病例包括 4 例源于 PA 的 SDC、8 例有 HN 的 SDC 和 5 例“新发”SDC。总共存在 23 例源于 PA 的 SDC(52.3%)。所有 6 例源于 LGCCC 的 SDC 均为 FISH 阴性。LGCCC 周围均有肌上皮染色,其中 17 例显示 DCIS。11 例 DCIS 病变位于源于 PA 的 SDC 或 FISH 阳性的“新发”SDC 中。这些病例代表导管的“癌变”。仅 6 例 FISH 阴性的“新发”SDC 出现 DCIS。

结论

很大一部分 SDC 起源于 PA(有或无 PA 的残余证据)。一小部分 SDC 起源于 LGCCC。表现为 DCIS 的病例常代表癌变。

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