Invasive mucinous adenocarcinoma of the lungs versus mixed invasive mucinous and non-mucinous adenocarcinoma:a clinicopathological analysis / 临床与实验病理学杂志

ABSTRACT

Purpose To investigate the clinicopathological characteristics,diagnosis,and differential diagnosis of invasive mucinous adenocarcinoma(IMA)and mixed invasive mucinous and non-mucinous adenocarcinoma(mIMA).Methods The clinical data were collected in 36 patients with primary IMA and 17 patients with mIMA,and the expression of TTF-1,CK7,CK20,SATB2,CDX2,EGFR,HNF4a,etc.was detected by immunohistochemical EnVision two-step method.The Sanger se-quencing and the FISH were used for KRAS mutation and NRG1 gene rearrangement detection.The clinicopathological character-istics were analyzed with review of relevant literature.Results There were 9 cases(25.0％)and 3(8.3％)cases of papillary and micropapillary structures in IMA,while 13 cases(76.5％)(P＜0.001)and 9 cases(52.9％)(P=0.001)were present in mIMA.There were 5 cases(13.9％)of high nuclear grade of IMA and 10 cases(58.8％)of high nuclear grade of mIMA(P=0.002).TTF-1 had a positive rate of 37.5％in IMA,but 60.0％and 80.0％in the mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA(P=0.021),respectively.The positive rates of CK7,CK20,and CDX2 in IMA were 90.6％,21.9％,and 9.4％,and the positive rates in mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA were 100％,20％,20％and 100％,6.7％,6.7％,respectively and no SATB2 expression was found in all cases.There was no significant difference in the expres-sion of total EGFR and two EGFR mutation-specific antibodies(L858R,DEL19)between IMA and mIMA.There were 3 cases of mucinous adenocarcinoma with L858R positive in mIMA,and 2 of them were negative for non-mueinous adenocarcinoma.In another case,the non-mueinous adenocarcinoma component of mIMA expressed DEL19,but the mucinous adenocarcinoma component was not expressed.The positive rate of HNF4a in IMA was 72.0％(18/25),and those of HNF4a in mucinous adenocarcinoma and non-mucinous adenocarcinoma in mIMA were 41.7％(5/12)and 33.3％(4/12),respectively(P=0.048).KRAS gene sequencing was carried out in 19 cases of IMA,among which 9 cases(47.4％)had mutations,G12D and G12V were most commonly detected,and 4 cases of mIMA were sequenced,but none of them showed KRAS mutations.FISH detection showed that 2 cases(7.1％)IMAs had NRG1 translocation rearrangement.Conclusion Pulmonary mIMA is more aggressive than IMA.For example,mIMA has significantly more papillary structure,micropapillary structure,and high nu-clear grade cases than IMA.The differences in immunohisto-chemical expression and KRAS mutation between the two are sta-tistically significant.