Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.
Hum Pathol. 2018 Jan;71:8-19. doi: 10.1016/j.humpath.2017.08.002. Epub 2017 Aug 17.
Invasive mucinous adenocarcinoma is a variant of lung adenocarcinoma, which may be mixed with nonmucinous adenocarcinoma. KRAS mutations are common, but other clinical and genetic features are not clearly established. Lung adenocarcinomas (n=760) with ≥5 years of follow-up comprised 3 nonoverlapping cohorts for survival analysis. Mucinous tumors were evaluated with Ion AmpliSeq Cancer Hotspot Panel v2. Cases without detected mutations were tested for ALK and ROS1 and by OncoScan array. Fifty-seven invasive mucinous adenocarcinomas and 54 mixed mucinous/nonmucinous adenocarcinomas were identified. Mucinous tumors constituted 27 of 218 nonselected patients (12.4%), 23 of 268 never-smokers (8.6%), and 61 of 274 in a smokers cohort enriched for lepidic growth (22.3%). In the lepidic-enriched smokers, patients with mucinous tumors experienced worse overall survival (P=.006) and progression-free survival (P=.024), which persisted on multivariable analysis. No survival differences were observed in the other cohorts. KRAS mutations were common (76% of invasive mucinous adenocarcinomas, 68% of mixed mucinous/nonmucinous), and 38% of KRAS mutations occurred with other mutations, especially STK11. Six cases had potentially targetable mutations (3 ALK, 2 EGFR, 1 BRAF V600E). All ALK-rearranged tumors were mixed mucinous/nonmucinous. Four of 6 cases without hotspot mutations showed complex copy number/structural abnormalities. Pulmonary invasive mucinous adenocarcinomas and mixed nonmucinous/mucinous adenocarcinomas are clinically and genetically similar, except for a higher rate of ALK rearrangement in mixed tumors. Survival for mucinous tumors is similar to that for nonmucinous tumors in a nonselected cohort, although worse survival was seen in a cohort of smokers enriched for lepidic growth.
浸润性黏液性腺癌是肺腺癌的一种变异型，可能与非黏液性腺癌混合存在。KRAS 突变很常见，但其他临床和遗传特征尚不清楚。对具有≥5 年随访的肺腺癌（n=760）进行了 3 个无重叠队列的生存分析。黏液性肿瘤用 Ion AmpliSeq Cancer Hotspot Panel v2 进行评估。未检测到突变的病例进行 ALK 和 ROS1 检测和 OncoScan 阵列检测。共鉴定出 57 例浸润性黏液性腺癌和 54 例混合性黏液/非黏液性腺癌。黏液性肿瘤在 218 例未选择患者中占 27 例（12.4%），在 268 例从不吸烟患者中占 23 例（8.6%），在富含贴壁生长的 274 例吸烟者队列中占 61 例（22.3%）。在贴壁生长丰富的吸烟者中，黏液性肿瘤患者的总生存（P=.006）和无进展生存（P=.024）更差，多变量分析仍如此。在其他队列中未观察到生存差异。KRAS 突变很常见（浸润性黏液性腺癌 76%，混合性黏液/非黏液性腺癌 68%），38%的 KRAS 突变与其他突变同时发生，尤其是 STK11。6 例有潜在的靶向突变（3 例 ALK，2 例 EGFR，1 例 BRAF V600E）。所有 ALK 重排肿瘤均为混合性黏液/非黏液性。6 例无热点突变的病例中，有 4 例显示复杂的拷贝数/结构异常。肺浸润性黏液性腺癌和混合性非黏液性/黏液性腺癌在临床和遗传学上相似，除了混合肿瘤中 ALK 重排的发生率更高。在非选择队列中，黏液性肿瘤的生存与非黏液性肿瘤相似，尽管在富含贴壁生长的吸烟者队列中观察到生存较差。
