Clinicopathological And Genetic Characteristics Of Peripheral And Central Pulmonary Squamous Cell Carcinoma

Objective:To investigate the the differences of clinicopathological and immunohistochemical characteristics and analyze gene mutation between peripheral-type(P-SQCC)and central-type(C-SQCC)lung squamous cell carcinoma.Methods:We reviewed patients who underwent surgical resection at the General Hospital of Eastern Theater Command from January 2013 to January 2018,eliminating patients who had preoperative malignant tumor history or received chemical/radial therapy.As a result,68 cases of P-SQCC and 62 C-SQCC were carefully selected respectively according to the following criteria:radiography,examination with the location of the tumor in surgical specimens and obeservation about the normal tissue around the tumor in light microscopy.Age,gender,smoking history,lymph node status,visceral pleural invasion,angiolymphatic invasion were evaluated in both groups,clinical stage and tumor size were stratified according to the American Joint Committee on Cancer,8th edition.P-SQCC were grouped into 3 subtypes based on the tumor growth pattern and the condition of elastic framework:combined type(alveolar space-filling dominant type),comined type(expanding growth dominant type)and expanding growth type.The most representative and distinctive tumor areas for C-SQCC and P-SQCC were evaluated to be sampled for tissue microarray(TMA),analyzing with a panel of antibodies inculding TTF-1(clone:8G7G3/1 and SPT24),NapsinA,P63,P40 and CK5/6.FGFR1 amplification was detected in TMA by fluorescence in situ hybridization(FISH).The mutations of exons 18,19,20 and 21 of EGFR gene,exons 2 and 3 of KRAS gene and exons 9 and 20 of PIK3CA gene were investigated by polymerase chain reaction(PCR)in 40 samples of P-SQCC and C-SQCC respectively.Twenty specimens of squamous epithelial cells in tracheal margin and twenty specimens of normal lung tissue were carefully selected as control groups individually.Results:(1)Histologic features:P-SQCC could be classified into 3 subgroups in histology including 13 cases of combined type(alveolar-space filling dominant type),23 cases of combined type(expanding growth dominant type)and 32 cases of expanding growth type according to growth pattern of tumor cells,and the ratio was 19%,34%,47%individually.(2)Clinicopathological features:P-SQCC patients were older than C-SQCC at the time of tumor resection,and there was no significant difference in gender,smoking history,clinical stage,tumor size,lymph node metastasis,pleural invasion,angiolymphatic invasion between two groups.There was no difference in overall survival and progression-free survival between the two groups.Alveolar space-filling ratio was a favorable prognostic factor in P-SQCC.(3)Immunohistochemistry:NapsinA and TTF-1(clone:8G7G3/1 and SPT24)were negative in all cases of P-SQCC and C-SQCC.There was no significant difference in the staining intensity of CK5/6,P63 and P40 between P-SQCC and C-SQCC,the P value was 0.190,0.233 and 0.632 individually.(4)Gene mutations:For PIK3CA gene,there were two E545K mutations in exon 9 and one H1047L mutation in exon 20 in P-SQCC;only one L858R mutation in exon 21 of EGFR gene was found in 1 case of C-SQCC.No mutation was detected in exon 2,3 of KRAS gene and 18,19,20 of EGFR gene in all samples.The control groups were all negative in mutation.With regard to TMA,there were clear signals in 27 cases of C-SQCC and 28 cases of P-SQCC.No survial difference was detected between the C-SQCC and P-SQCC(P=0.679),for the occurrence of 6 and 4 cases of C-SQCC and P-SQCC show amplification respectively.Conclusion:(1)As to histologic subtype of P-SQCC,the alveolar-space filling subtype was expected to be a favorable marker in prognosis.(2)There was a significantly older age in P-SQCC than C-SQCC,however,no significant statistical difference in smoking history,clinical stage,tumor size,lymph node metastasis,pleural invasion and angiolymphatic invasion was observed between the two groups.OS and PFS were not significantly dififerent between P-SQCC and C-SQCC.(3)There is no difference between P-SQCC and C-SQCC in immunohistochemical antibody staining including NapsinA,TTF-1(8G7G3/1 and SPT24),CK5/6,P63,P40.(4)Analysis of gene mutation show strongly difference between P-SQCC and C-SQCC,as a result of the hotspot mutation of PIK3CA gene was exclusively detected in P-SQCC.We found a trend toward longer survival among patients with FGFR1 amplification in both groups despite lack of statisticial difference,indicating that FGFR1 amplification might suggest survival advantage.