Department of Pathology, Fudan University Shanghai Cancer Center, Fudan University, 270 Dong An Road, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China.
Diagn Pathol. 2019 Aug 28;14(1):96. doi: 10.1186/s13000-019-0864-7.
Ovarian metastatic tumors from lung adenocarcinoma are rare, and a serial study of these tumors is lacking to date. Additionally, a better understanding of the clinicopathological and molecular characteristics of metastatic tumors is needed.
Seven cases of ovarian metastasis from lung adenocarcinoma from 2013 to 2017 at our institute were investigated. The results were combined with those found in literature review. A total of 16 cases were analyzed in the present study. We examined clinicopathological and immunohistochemical characteristics, further detected ALK rearrangement by FISH (fluorescence in situ hybridization), and assessed EGFR and KRAS mutations using Sanger sequencing or the amplification refractory mutation system (ARMS).
The mean age of the patients was 44.6 years (range, 33-56 years). Eleven of sixteen patients developed ovarian tumors within a mean time of 18.5 months (range, 5-48 months) from the initial diagnosis of lung adenocarcinoma; 5 patients had lung tumors and ovarian masses simultaneously. Five tumors (5/16, 31%) occurred in the bilateral ovaries, and the others were unilateral ovarian tumors (11/16, 69%). All seven cases from our institute were positive for TTF-1 and Napsin A but negative for PAX8. In four cases, ALK (D5F3) was diffusely and strongly expressed, with ALK rearrangements (4/7, 57%). Overall, ALK rearrangement was found by FISH or immunohistochemistry in 11/16 (69%) cases. In two cases, EGFR mutations in exons 19 and 21, respectively, were found. One patient did not detected EGFR or ALK mutation in the metastatic tumor, but the primary lung adenocarcinoma did harbor an EGFR mutation. Two cases had no alterations in three genes above. Although the mean survival time of the patients with ALK rearrangement was longer than those without (mean survival time 25 m vs. 20 m), no statistical significance of the difference was found.
As the largest case series of ovarian metastasis from lung adenocarcinoma, our findings indicate that ALK rearrangement is the most common molecular alteration. Although patients with ALK rearrangement appear to have a better prognosis than do those without ALK rearrangement, more cases with longer follow-up and multivariant analysis are needed to clarify this point.
来自肺腺癌的卵巢转移瘤较为罕见，目前尚无此类肿瘤的系列研究。此外，还需要更好地了解转移性肿瘤的临床病理和分子特征。
研究了 2013 年至 2017 年我院 7 例来自肺腺癌的卵巢转移瘤病例，并与文献复习结果相结合。共分析了 16 例病例。我们检测了临床病理和免疫组织化学特征，通过 FISH（荧光原位杂交）进一步检测 ALK 重排，并通过 Sanger 测序或扩增不可避免突变系统（ARMS）检测 EGFR 和 KRAS 突变。
患者的平均年龄为 44.6 岁（范围 33-56 岁）。16 例患者中有 11 例在肺腺癌初始诊断后 18.5 个月（范围 5-48 个月）内出现卵巢肿瘤；5 例患者同时有肺肿瘤和卵巢肿块。5 个肿瘤（5/16，31%）发生在双侧卵巢，其余为单侧卵巢肿瘤（11/16，69%）。我院的 7 例病例均为 TTF-1 和 Napsin A 阳性，但 PAX8 阴性。在 4 例中，ALK（D5F3）弥漫且强烈表达，存在 ALK 重排（4/7，57%）。总体而言，16 例中有 11 例（69%）通过 FISH 或免疫组化发现 ALK 重排。在 2 例中，分别发现了外显子 19 和 21 的 EGFR 突变。1 例患者在转移性肿瘤中未检测到 EGFR 或 ALK 突变，但原发性肺腺癌存在 EGFR 突变。2 例患者上述 3 个基因均无改变。ALK 重排患者的平均生存时间长于无 ALK 重排患者（平均生存时间 25m 比 20m），但差异无统计学意义。
作为最大的肺腺癌卵巢转移瘤病例系列，我们的研究结果表明 ALK 重排是最常见的分子改变。虽然有 ALK 重排的患者似乎比没有 ALK 重排的患者预后更好，但需要更多具有更长随访时间和多变量分析的病例来阐明这一点。
