| Objective To desplore the relation of age and the clinicalpathological characteristics and prognosis of primary lung adenocarcinoma.Materials Collected the clinical date of 436 patients who treated by surgical operation with primary lung adenocarcinoma from the First Affilication Hospital of Zheng Zhou University between 2013.01.01 and 2014.12.31.Methods Take the 50-years-old as the cutoff value,regard the patients who under 50 years old as ≤50-year group,while the patients who above 50 years old as the >50-year group.Comparatively analysised the result of clinicopathological characteristics,The gene phenotypes of EGFR and KRAS tested by ARMS-PCR method,and the protein expressions of ALK tested by immunohistochemisty(Ventana method)in the two age groups,and followed up their prognosis,thereby analysised the lelation ofage and the clinicalpathological characteristics,the gene phenotypes of EGFR and KRAS,ALK protein expressions and prognosis of primary lung adenocarcinoma.Results 1 General clinicalpathological characteristics 1.1 General clinicalpathological characteristics of the ≤50-year group group There were 95(21.8%)patients in the ≤50-year group: the mean age was 44.87±5.739 years old(range: 15-50 years old);44 female patients(46.3%),51 male patients(53.7%);72 non-somkers(75.8%),23 smokers(24.2%);there were 35 patients(36.8%)with tumor located in the left lung and 60 patients(63.2%)with tumor located in the right lung.The mean value of the maximum diameter of tumors was 33.87±18.366mm(range:5-85mm);14 patients(14.7%)had a family history of malignant tumors(including lung cancer).Histopathological classification: acinar type(n=30,31.6%),papillary type(n=25,26.3%),micropapillary type(n=14,14.7%),solid type(n=10,10.5%),lepid type(n=9,9.5%),invasive mucus type(n=7,7.4%).34patients(35.8%)occurred lymph node metastasis.c TNM staging: Stage I(n=44,46.3%),Stage II(n=28,29.5%),Stage III(n=23,24.2%).Surgical approach: 1 patient(1.1%)was treated by segmentectomy and 94 patients(98.9%)were treated by lobectomy.1.2 General clinicalpathological characteristics of the >50-year group There were 341 patients(78.2%)in the >50-year group: the mean age was 62.08±6.889 years old(range: 51-83 years old);175 female patients(51.3%)and 166 male patients(48.7%);217 nonsmokers(63.6%),124 smokers(36.4%);there were 139 patients(40.8%)with tumor located in the left lung and 202 patients(59.2%)with tumor located in the right lung;the mean value of maximum diameter of tumors was 31.72±19.061 mm(range:4-160 mm);54 patients(15.8%)had a family history of malignant tumors(including lung cancer).Histopathological classification: acinar type(n=114,33.4%),papillary type(n=101,29.6%),solid type(n=43,12.6%),lepid type(n=36,10.6%),invasive mucinous type(n=32,9.4%),micropapillary type(n=15,4.4%).77 patients(22.6%)occurred lymph node metastasis.c TNM staging: Stage I(n=205,60.1%),Stage II(n=88,25.8%),Stage III(n=48,14.1%).Surgical approach: 323 patients(94.7%)were treated by lobectomy,13 patients(3.8%)were treated by wedge resection,3 patients(0.9%)were treated by sleeve resection and 2 patients(0.6%)were treated by segmentectomy.1.3 Comparison of the general clinicalpathological characteristics between of the two age groups Non-smokers(P=0.027)were more common in the ≤50-year group;Gender(P=0.388),tumor location(P=0.490),the mean value of tumor maximal diameter(P=0.278),and the history of malignant tumor(P=0.794)were not statistically significant.The predominant micropapillary subtype was more common in the ≤50-year group than that in the >50-year group(P=0.024),while the distribution of other histological subtypes were not statistically significant(P=0.995).The lymph node metastasis rate(P=0.009)was higher in the ≤50-year group than that in the >50-year group.Patients with stage I and stage II were not statistically significant in the two age groups(P = 0.148),while the proportion of stage III patients in the ≤50-year group was greater than that in the >50-year group(P = 0.023).The surgical approach was also different in the two age groups: the ≤50-year group only treated by lobectomy resction;the >50-year group also were treated by wedge and sleeve resections(P=0.042),except for lobectomy and segment resection.2 Gene phenotypes of EGFR/KRAS detection and protein expressions of ALK immunohistochemisty 2.1 Results of Gene phenotypes of EGFR/KRAS detection and protein expressions of ALK immunohistochemisty163 patients were detected the gene phenotypes of EGFR tested by ARMS-PCR method,and the mutation rate of EGFR gene was 57.7%(n=94).There was no relation between EGFR mutation rate and gender(P=0.719),and there was no relation between EGFR mutation rate and smoking station(P=0.398).The gene phenotypes of EGFR: 19 exon deletion mutations(n=50,53.2%),21 exon L858 R mutations(n=39,41.5%)),18-G719 X mutation(n=2,2.1%),20 insertions mutation(n=2,2.1%),21-L861Q+18-G719 X mutation(n=1,1.1%).16 patients were detected the gene phenotypes of KRAS tested by ARMS-PCR method,the mutation rate of KRAS gene was 18.8%(n=3).There was no relation between KRAS mutation rate and gender(P=0.237),and there was no relation between KRAS mutation rate and smoking station(P=0.519).The gene phenotypes of KRAS: G12D(n=1,33.3%),G12 A.(n=1,33.3%),G12V(n=1,33.3%).129 patients were tested the protein expressions of ALK by immunohistochemisty(Ventana),12 were positive,the positive rate of protein expression of ALK was 9.3%.There was no relation between the rate of protein expression of ALK and gender(P=0.142),and there was no relation between the rate of the protein expression of ALK and smoking station(P=0.149).2.2 Comparison of gene phenotypes of EGFR/KRAS detection and protein expressions of ALK immunohistochemisty between the two groups The mutation rate of EGFR gene(P=0.487)and the gene phenotypes of EGFR(P=0.719)were not statistically significant between the two age groups.The KRAS mutation rate and the gene phenotypes of KRAS gene was not statistically significant between the two age groups(P=0.237).The gene phenotypes of KRAS gene was not statistically significant between the two age groups.The positive rate of protein expression of ALK in the two age groups were not statistically significant(P=0.800).3 Prognosis 3.1 Result of the follow-up As of December 31,2017,in the ≤50-year group,2 case was lost follow-up and 93 patients were followed up.Follow-up time range:2-59 months.39 cases weresurvived and 54 cased were died.The overall survival rate was 41.9%.The median survival period is 36 months.The mean survival period was 30.43±17.750 months(range:2-59 months).In the >50-year group,5 patients had no contact information and 341 patients were followed up.The range of follow-up time: 4-59 months.202 patients were survived and 134 patients were died.The median survival time was 42 months.The mean survival period was 37.69±14.643 months(range:4-59 months).3.2 Comparison of survival analysis between of the two age groups The overall survival rate was lower in the ≤50-year group than that in the >50-year group(P=0.002);the mean survival time was shorter in the ≤50-year group(P=0.000);Further analyzed the effects of age in different populations,the results showed that the prognosis of male(P=0.000),smokers(P=0.000),non-smokers(P=0.015),stage Ⅱ and Ⅲ(respectively: P=0.021,P=0.000),the patients with EGFR mutation(P=0.036)and the EGFR wild type(P=0.005),the patients with KRAS wild type(P= 0.041)and the patients with ALK-negative(P=0.042)in the ≤50-year group was poorer than that in the >50-year group.In the Cox regression model,the prognosis of primary lung adenocarcinoma patients who ≤ 50-year was significantly worse than the primary lung adenocarcinoma patients who >50-year(HR:0.537,95%CI:0.392-0.737,P=0.000),and age was the independent prognostic factor.Conclusion There were more non-smokers in the primary lung adenocarcinoma patients who were under 50 years old,and there were more patients with poor differentiation subtypes and advantaged stage in the ≤50-year group,and more likely to happen lymph node metastasis,thus the prognosis in the patients who were under 50 years old was poorer than that in the patients who were older than 50 years. |
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