Dacic Sanja, Finkelstein Sydney D, Baksh Fabien K, Swalsky Patricia A, Barnes Leon E, Yousem Samuel A
Department of Pathology, Division of Anatomic Pathology, University of Pittsburgh Medical Center, Presbyterian University Hospital, PA 15213, USA.
Hum Pathol. 2002 Sep;33(9):927-32. doi: 10.1053/hupa.2002.126875.
Small-cell neuroendocrine carcinoma (SCNC) is a well characterized malignancy with distinctive cellular morphology and aggressive biologic behavior most frequently encountered in the lung but also noted for origin from other sites. The basis for this difference in incidence and the impact of primary site location on the molecular pathogenesis of the neoplasm is not well understood. To address this issue and to identify reliable molecular markers of potential diagnostic value for primary site localization of this tumor, we have compared the genetic profile of cancer-related gene damage of SCNC arising from a variety of organ sites. The analysis involved microdissected paraffin-embedded formalin fixed specimens of SCNC. Tumors were organized into 3 groups: lung (n = 18), head and neck region (n = 5), and gastrointestinal tract (n = 5). Genotyping evaluated allelic imbalance (loss of heterozygosity) involving genomic regions containing p53 (17p13), L-myc (1p34), OGG1 (3p26), MCC/APC (5q21), p16 (9p21), PTEN (10q23), and point mutational change in K-ras-2 (12p12) using polymerase chain reaction-based microsatellite analysis and DNA sequencing. Distinct genotypic profiles of allelic imbalance using this panel was seen for each group of SCNC enabling primary site determination to be suggested based on genotypic profiling of microdissected tissue samples. Despite similarity in histologic appearance, our study suggests that SCNC have a unique pattern of acquired allelic damage that is determined in part by primary site of tumor development. These attributes can be effectively used for primary localization of metastatic SCNC, thereby assisting in the diagnosis and classification of this neoplasm.
小细胞神经内分泌癌（SCNC）是一种特征明确的恶性肿瘤，具有独特的细胞形态和侵袭性生物学行为，最常见于肺部，但也可见于其他部位起源的病例。目前对于这种发病率差异的原因以及原发部位对肿瘤分子发病机制的影响尚不清楚。为了解决这个问题并确定对该肿瘤原发部位定位具有潜在诊断价值的可靠分子标志物，我们比较了源自不同器官部位的SCNC的癌症相关基因损伤的基因谱。分析涉及经显微切割的石蜡包埋、福尔马林固定的SCNC标本。肿瘤分为3组：肺（n = 18）、头颈部区域（n = 5）和胃肠道（n = 5）。使用基于聚合酶链反应的微卫星分析和DNA测序对涉及包含p53（17p13）、L-myc（1p34）、OGG1（3p26）、MCC/APC（5q21）、p16（9p21）、PTEN（10q23）的基因组区域的等位基因失衡（杂合性缺失）以及K-ras-2（12p12）的点突变变化进行基因分型评估。每组SCNC均可见使用该检测板得出的不同等位基因失衡基因型谱，从而能够根据显微切割组织样本的基因型分析来推断原发部位。尽管组织学外观相似，但我们的研究表明，SCNC具有独特的获得性等位基因损伤模式，部分由肿瘤发生的原发部位决定。这些特征可有效地用于转移性SCNC的原发定位，从而有助于该肿瘤的诊断和分类。
