Vinciguerra Gian Luca Rampioni, Scarpino Stefania, Pini Benedetto, Cippitelli Claudia, Fochetti Flavio, Ruco Luigi
Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Rome, Italy.
Virchows Arch. 2017 Jul;471(1):123-127. doi: 10.1007/s00428-017-2145-8. Epub 2017 May 17.
We used optimized immunohistochemistry (IHC) with the D5F3 antibody for detection of tumours in a prospective study of 307 pulmonary adenocarcinomas. Cases positive by IHC (1+, 2+, 3+) were further investigated by fluorescent in situ hybridization (FISH). Of 307 cases, 22 (7.2%) were moderately intensely positive (2+/3+); 18 of these (82%) were also positive by FISH. Of the four IHC-positive/FISH-negative cases, one was unsuitable for FISH and three had abnormalities of the ALK gene. All cases with weak reactivity with D5F3 (1+) were FISH-negative. The FISH positive/IHC-positive cases with moderately intense reactivity had the typical clinicopathologic features of ALK-positive patients (younger age, p < 0.01; higher frequency in metastatic sites, p < 0.01; cribriform/mucinous/signet histology, p < 0.01; stage IV disease, p < 0.01). In conclusion, our findings indicate that optimized IHC using the D5F3 antibody provides a reliable and inexpensive test for identification of ALK-positive adenocarcinomas. Inclusion of this information in the pathology report at the time of the histological diagnosis might significantly shorten time to treatment.
在一项对307例肺腺癌的前瞻性研究中，我们使用优化后的免疫组织化学（IHC）方法，采用D5F3抗体检测肿瘤。免疫组化呈阳性（1+、2+、3+）的病例通过荧光原位杂交（FISH）进一步检测。在307例病例中，22例（7.2%）呈中度强阳性（2+/3+）；其中18例（82%）FISH检测也呈阳性。在4例免疫组化阳性/FISH阴性的病例中，1例不适合进行FISH检测，3例存在ALK基因异常。所有与D5F3呈弱反应性（1+）的病例FISH检测均为阴性。FISH阳性/免疫组化阳性且反应强度为中度的病例具有ALK阳性患者典型的临床病理特征（年龄较小，p<0.01；转移部位发生率较高，p<0.01；筛状/黏液性/印戒样组织学，p<0.01；IV期疾病，p<0.01）。总之，我们的研究结果表明，使用D5F3抗体进行优化后的免疫组化可为识别ALK阳性腺癌提供一种可靠且廉价的检测方法。在组织学诊断时将此信息纳入病理报告可能会显著缩短治疗时间。
