Clinical Features And Prognostic Significance Of Pulmonary Adenocarcinoma With A Micropapillary Pattern

Objective:In the world,cancer has become the second most important disease that causes death worldwide.According to the 2018 Global Cancer Database,lung cancer accounts for the first incidence of all cancers,and it is also the main cause of cancer death.In recent years,micropapillary predominant adenocarcinoma(MPA)has attracted attention because of its high invasiveness and poor prognosis.Therefore,in2011,the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society(IASLC/ATS/ERS)proposed to use MPA as a new subtype of lung adenocarcinoma.Pulmonary adenocarcinoma with a micropapillary(MPPAC)which occurs rarely is a subtype of invasive lung adenocarcinoma.MPPAC has received attention in recent years due to its high vascular metastasis rate,lymph node metastasis rate,and poor prognosis.The purpose of this study is to make a retrospective analysis on the clinicopathological characteristics of MPPAC and its effect on prognosis,and thus,improve clinicians understanding of MPPAC.Methods:We reviewed 366 consecutive cases of lung adenocarcinomas that had been surgically resected at Fu Jian Provincial Hospital from January 1,2013 to December31,2018,and divided it into two groups,one was called MPPAC group,and the other was called lung adenocarcinoma without micropapillary pattern.The time of recurrence or death was obtained through telephone or in-hospital follow-up,and the deadline was December 31,2019.Clinical data collected and analyzed included:gender,age,BMI,clinical symptoms,smoking status,TNM classification,distant metastasis,vascular invasion,lymph node metastasis,micropapillary pattern content,epidermal growth factor receptor genetic detection,Progresion-Free Survival(PFS)and Overall Survival(OS),etc.Chi-square test was used to investigate the clinicopathological characteristics between MPPAC group and control group,or between the three subgroups of the MPPAC group.Survival analysis(Kaplan-Meier survival time curve)was used to evaluate the prognosis of MPPAC,and univariate and multivariate COX regression models were used to predict the factors influencing the prognosis of MPPAC.Results:Compared with the control group,the MPPAC group has the following clinical characteristics: the overall mean BMI is lower,and vascular metastasis and distant metastasis are easier to occur,high expression of Ki-67.MPPAC is significantly lower in PFS than the control group(85.7%,57.9%,40.1%,1-year,3-year,and 5-year PFS,respectively).And there was no significant difference in OS between MPPAC and the control group.In different subgroups of MPP content contrast(group one: MPP≤5%,a total of 69 cases;group two: 5%<MPP<50%,a total of 103 cases;Group three: MPP≥50%,a total of 11 cases),we can make a conclusion that the higher content of MPP is related to the higher the ratio of the largest tumor diameter> 3cm,the higher the rate of vascular invasion,the higher the rate of lymph node metastasis,easier to relapse,diagnosis and follow-up period appeared distant metastasis rate is higher,the greater proportion of clinical stages above Ⅱ.What’s more,the bidirectional ordered Spearman rank sum test suggest that there is a significant positive correlation between MPP content and prognosis.Univariate prognostic analysis(PFS)showed that lower BMI,tumor diameter﹥3 cm,lymph node metastasis positive,EGFR mutation negative,high Ki-67 expression,higher content of MPP are correlate with poor PFS.Multivariate analysis(PFS)showed that lymph node metastasis [P=0.002,HR=2.539(95%CI: 1.379-4.036)] and Ki-67 [P=0.021,HR=1.397(95%CI: 1.053-1.853)] were independent risk factors for PFS in MPPAC patients.Univariate prognostic analysis(OS)showed that non-physical examination findings,vascular invasion positive,lymph node metastasis positive,EGFR mutation wild-type,higher content of MPP,patients with distant metastasis,the greater number of distant metastases are correlate with worse OS.Multivariate analysis showed that physical examination [P=0.003,HR=0.323(95%CI: 0.155-0.674)],MPP content[P=0.006,HR=2.28(95%CI: 1.261-4.121)] and number of distant metastatic organs[P=0.001,HR=3.485(95%CI: 1.714-7.087)] are independent risk factors for OS.Number of distant metastases.Conclusion:MPPAC has a poor prognosis due to its high rate of vascular metastasis,high rate of lymph node metastasis,high rate of distant metastasis and high recurrence rate.This study analyzed the clinical characteristics of MPPAC:the mean BMI is low,vascular metastasis and distant metastasis are easier to occur,high expression of Ki-67 in immunohistochemistry.But there is no significant difference in EGFR gene mutation between MPPAC and lung adenocarcinoma without micropapillary pattern group.The higher content of MPP is related to the higher the ratio of the largest tumor diameter> 3cm,the higher the rate of vascular invasion,the higher the rate of lymph node metastasis,easier to relapse,diagnosis and follow-up period appeared distant metastasis rate is higher,the greater proportion of clinical stages above Ⅱ.What’s more,the bidirectional ordered Spearman rank sum test suggest that there is a significant positive correlation between MPP content and prognosis.Multivariate survival analysis show that lymph node metastasis and ki-67 are independent risk factors for PFS.Physical examination find to be an independent protective factor for OS.MPP content and number of distant metastatic organs are independent risk factors for OS.