Greco F Anthony, Lennington Wayne J, Spigel David R, Hainsworth John D
Sarah Cannon Research Institute and Cancer Center, Tennessee Oncology, PLLC, Suite 100, 250 25th Avenue North, Nashville, TN, 37203, USA,
Mol Diagn Ther. 2015 Apr;19(2):91-7. doi: 10.1007/s40291-015-0133-8.
Definition of the lineage of poorly differentiated neoplasms (PDNs) presenting as cancer of unknown primary site (CUP) is important since many of these tumors are treatment-sensitive. Gene expression profiling and a molecular cancer classifier assay (MCCA) may provide a new method of diagnosis when standard pathologic evaluation and immunohistochemical (IHC) staining is unsuccessful.
Thirty of 751 CUP patients (4%) seen from 2000-2012 had PDNs without a definitive lineage diagnosed by histology or IHC (median 18 stains, range 9-46). Biopsies from these 30 patients had MCCA (92-gene reverse transcriptase-polymerase chain reaction mRNA) performed. Additional IHC, gene sequencing, fluorescent in situ hybridization for specific genetic alterations, and repeat biopsies were performed to support MCCA diagnoses, and clinical features correlated. Seven patients had MCCA performed initially and received site-specific therapy.
Lineage diagnoses were made by MCCA in 25 of 30 (83 %) patients, including ten carcinomas (three germ cell, two neuroendocrine, five others), eight sarcomas [three peritoneal mesotheliomas, one primitive neuroectodermal tumor (PNET), four others], five melanomas, and two lymphomas. Additional IHC and genetic testing [BRAF, i(12)p] supported the MCCA diagnoses in 11 of 16 tumors. All seven patients (two germ cell, two neuroendocrine, two mesothelioma, one lymphoma) responded to site-specific therapy based on the MCCA diagnosis, and remain alive (five progression-free) from 25+ to 72+ months.
The MCCA provided a specific lineage diagnosis and tissue of origin in most patients with PDNs unclassifiable by standard pathologic evaluation. Earlier use of MCCA will expedite diagnosis and direct appropriate first-line therapy, which is potentially curative for several of these tumor types.
明确表现为原发部位不明癌（CUP）的低分化肿瘤（PDN）的谱系很重要，因为这些肿瘤中有许多对治疗敏感。当标准病理评估和免疫组化（IHC）染色无法确诊时，基因表达谱分析和分子癌症分类检测（MCCA）可能提供一种新的诊断方法。
2000年至2012年间诊治的751例CUP患者中有30例（4%）患有PDN，其组织学或IHC检查均未明确谱系（中位数18次染色，范围9 - 46次）。对这30例患者的活检标本进行了MCCA检测（92基因逆转录聚合酶链反应mRNA检测）。还进行了额外的IHC、基因测序、针对特定基因改变的荧光原位杂交以及重复活检以支持MCCA诊断，并对临床特征进行了关联分析。7例患者最初进行了MCCA检测并接受了针对特定部位的治疗。
30例患者中有25例（83%）通过MCCA明确了谱系诊断，包括10例癌（3例生殖细胞癌、2例神经内分泌癌、5例其他癌）、8例肉瘤（3例腹膜间皮瘤、1例原始神经外胚层肿瘤（PNET）、4例其他肉瘤）、5例黑色素瘤和2例淋巴瘤。额外的IHC和基因检测[BRAF，i(12)p]在16例肿瘤中的11例支持了MCCA诊断。所有7例患者（2例生殖细胞癌、2例神经内分泌癌、2例间皮瘤、1例淋巴瘤）根据MCCA诊断接受了针对特定部位的治疗，并且存活至今（5例无进展），时间从25个月以上至72个月以上。
对于大多数经标准病理评估无法分类的PDN患者，MCCA提供了特定的谱系诊断和组织来源。更早使用MCCA将加快诊断并指导合适的一线治疗，其中几种肿瘤类型可能通过这种治疗治愈。
