| Background:With the development of enhanced recovery after surgery,clinical strategies for the non-small cell lung cancer(NSCLC)patients with clinical stage T1a-c are also evolving.Segmentectomy or subsegmentectomy combine with selective lymph node dissection has gradually replaced radical lobectomy as a standard surgical procedure due to its unique advantages of reduced trauma.faster recovery,and improved surgical outcomes.Nevertheless,some NSCLC patients still develop occult lymph node metastasis(OLNM)at clinical T1 stage,making determining suitable surgical strategies challenging.Micropapillary predominant(MCP)adenocarcinoma has been considered an independent risk parameter for lymphatic metastasis and recurrence owing to its high invasivity and poor prognosis.However,nonpredominant micropapillary patterns(NP-MCP)is a more common subtype than MCP,micropapillary component of NP-MCP is not less than 5%but it does not meet the MCP diagnostic criteria.At present,there are still few studies on NP-MCP.The genetic alterations in NP-MCP patients and genetic traits responsible for OLNM have not been elucidated.And a prediction model for preoperative OLNM risk needs to be developed to guide clinical treatment decision-making and improve patient prognosis.Methods:Between January 2019 and December 2021,6418 patients who underwent complete resection for primary lung adenocarcinoma at the Qilu Hospital of Shandong University.After the secondary screening,442 patients diagnosed with lung adenocarcinoma with NP-MCP with a tumor size ≤3 cm were included.Genetic alterations were analyzed using amplification refractory mutation system-polymerase chain reaction(ARMS-PCR).Abnormal protein expression of gene mutations was validated using immunohistochemistry(IHC).Clinicopathological data were collected from the patient medical record management system.SPSS Statistics software was utilized to conduct Logistic univariate and multivariate regression analyses.Independent risk factors in NP-MCP patients for OLNM were then determined by statistical analyses.The nomogram risk prediction model was constructed using R studio software after screening risk factor variables.Calibration plots were performed to evaluate the model compliance.The receiver operating characteristic curves(ROC)of model and independent risk variables was calculated by using GraphPad Prism software to evaluate the predictive ability.Results:In our retrospective cohort,the incidence rate of the micropapillary component was 11.17%,and OLNM was observed in 20.13%of the patients in our study.ARMS-PCR suggested that EGFR exon 19 del was the most frequent alteration in NP-MCP patients compared with other gene mutations(frequency:21.2%,P<0.001).Patients harboring exon 19 del showed significantly higher risk of OLNM(P<0.001).Multivariate logistic regression analysis showed that age(OR=0.96;95%CI:0.93-0.99;P=0.006),tumor size(OR=1.89;95%CI:1.26-2.97;P=0.005),CYFRA21-1 level(OR=1.66;95%CI:1.39-2.00;P<0.001),micropapillary component(OR=1.03;95%CI:1.01-1.05;P=0.001)and solid component(OR=1.04;95%CI:1.04-1.07;P=0.001)were independent risk factors for OLNM in nonpredominant micropapillary component patients.A nomogram was developed based on five risk parameters,which showed good calibration and reliable discrimination ability(C-index=0.84)for evaluating OLNM risk.Conclusions:Intense expression of EGFR exon 19 del characterizes lung adenocarcinoma in patients with NP-MCP and it’s a potential risk factor for OLNM.We firstly established a nomogram based on age,CYFRA21-1 level,tumor size,micropapillary and solid composition,that was effective in predicting OLNM among NP-MCP of lung adenocarcinoma measuring≤3 cm. |
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