Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.

INTRODUCTION: HNF4α expression and SMARCA4 loss were thought to be features of non-terminal respiratory unit (TRU)-type lung adenocarcinomas, but their relationships remained unclear. MATERIALS AND METHODS: HNF4α-positive cases among 241 lung adenocarcinomas were stratified based on TTF-1 and SMARCA4 expressions, histological subtypes, and driver mutations. Immunohistochemical analysis was performed using xenograft tumors of lung adenocarcinoma cell lines with high HNF4A expression. RESULT: HNF4α-positive adenocarcinomas(n = 33) were divided into two groups: the variant group(15 mucinous, 2 enteric, and 1 colloid), where SMARCA4 was retained in all cases, and the conventional non-mucinous group(6 papillary, 5 solid, and 4 acinar), where SMARCA4 was lost in 3/15 cases(20%). All variant cases were negative for TTF-1 and showed wild-type EGFR and frequent KRAS mutations(10/18, 56%). The non-mucinous group was further divided into two groups: TRU-type(n = 7), which was positive for TTF-1 and showed predominantly papillary histology(6/7, 86%) and EGFR mutations(3/7, 43%), and non-TRU-type(n = 8), which was negative for TTF-1, showed frequent loss of SMARCA4(2/8, 25%) and predominantly solid histology(4/8, 50%), and never harbored EGFR mutations. Survival analysis of 230 cases based on histological grading and HNF4α expression revealed that HNF4α-positive poorly differentiated (grade 3) adenocarcinoma showed the worst prognosis. Among 39 cell lines, A549 showed the highest level of HNF4A, immunohistochemically HNF4α expression positive and SMARCA4 lost, and exhibited non-mucinous, high-grade morphology in xenograft tumors. CONCLUSION: HNF4α-positive non-mucinous adenocarcinomas included TRU-type and non-TRU-type cases; the latter tended to exhibit the high-grade phenotype with frequent loss of SMARCA4, and A549 was a representative cell line.

Clinical outcomes of left upper segmentectomy vs. lobectomy for early non-small-cell lung cancer: a nationwide database study in Japan.

PURPOSE: Given that left upper lobe and right upper and middle lobes share a similar anatomy, segmentectomy, such as upper division and lingulectomy, should yield identical oncological clearance to left upper lobectomy. We compared the prognosis of segmentectomy with that of lobectomy for early stage non-small-cell lung cancer (NSCLC) in the left upper lobe. METHODS: We retrospectively examined 2115 patients who underwent segmentectomy or lobectomy for c-stage I (TNM 8th edition) NSCLC in the left upper lobe in 2010. We compared the oncological outcomes of segmentectomy (n = 483) and lobectomy (n = 483) using a propensity score matching analysis. RESULTS: The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were comparable, irrespective of c-stage IA or IB. Subset analyses according to radiological tumor findings showed that segmentectomy yielded oncological outcomes comparable to those of lobectomy for non-pure solid tumors. In cases where the solid tumor exceeded 20 mm, segmentectomy showed a recurrence-free survival inferior to that of lobectomy (p = 0.028), despite an equivalent overall survival (p = 0.38). CONCLUSION: Segmentectomy may be an acceptable alternative to lobectomy with regard to the overall survival of patients with c-stage I NSCLC in the left upper lobe.

Contralateral pneumothorax with postpneumonectomy syndrome: report of 18-year-old case.

We herein report a case of an 18-year-old male with left postpneumonectomy syndrome who underwent a bullectomy for right pneumothorax. The patient underwent a left pneumonectomy at the age of 1 year. At the age of 18 years, he developed right pneumothorax, and radiological findings revealed apical bullae in the right pleural cavity extending into the left atrophic thoracic cavity beyond the upper mediastinum. The right thoracoscopic bullectomy was successful. Modifications of selective lobar ventilation during surgery and thoracoscope position were described.

Matrix metalloproteinase­1 and microRNA­486­5p in urinary exosomes can be used to detect early lung cancer: A preliminary report.

The present study describes a novel molecular-genetic method suitable for lung cancer (LC) screening in the work-place and at community health centers. Using urinary-isolated exosomes from 35 patients with LC and 40 healthy volunteers, the expression ratio of MMP-1/CD63, and the relative expression levels of both microRNA (miRNA)-21 and miRNA-486-5p were measured. MMP-1/CD63 expression ratio was significantly higher in patients with LC than in the healthy controls {1.342 [95% confidence interval (CI): 0.890-1.974] vs. 0.600 (0.490-0.900); P<0.0001}. The relative expression of miRNA-486-5p in male healthy controls was significantly different from that in female healthy controls, whereas there was no significant difference in miRNA-21. Receiver operating characteristic curve (ROC) analysis of MMP-1/CD63 showed 92.5% sensitivity and 54.3% specificity, whereas miRNA-486-5p showed 85% sensitivity and 70.8% specificity for men, and 70.0% sensitivity and 72.7% specificity for women. The logistic regression model used to evaluate the association of LC with the combination of MMP-1/CD63 and miRNA-486-5p revealed that the area under the ROC curve was 0.954 (95% CI: 0.908-1.000), and the model had 89% sensitivity and 88% specificity after adjusting for age, sex and smoking status. These data suggested that the combined analysis of MMP-1/CD63 and miRNA-486-5p in urinary exosomes may be used to detect patients with early-stage LC in the work-place and at community health centers, although confirmational studies are warranted.

Computational study on hemodynamic effects of left superior pulmonary vein resection and associated physiological changes in the left atrium after left upper lobectomy.

Left upper lobectomy (LUL) with left superior pulmonary vein (LSPV) resection alters the left atrium (LA) physiological states and LA hemodynamics associated with thrombosis, although this underlying mechanism is poorly understood. Therefore, we investigated the effects of LSPV resection and associated LA physiological changes on LA hemodynamics using four-dimensional computed tomography image-based computational simulations. Three cases were considered: the LA before and after LUL extracted from computed tomography images and artificial LSPV resection without physiological changes. Comparisons among the three cases demonstrated that physiological changes associated with LSPV resection are the possible factors that affect the LA hemodynamics after LUL.

Benefit of Adjuvant Chemotherapy for Patients Older Than 75 Years With Completely Resected p-Stage II-IIIA Non-Small-Cell Lung Cancer: A Retrospective Cohort Study Using Japanese Nationwide Real-World Data.

BACKGROUND: The efficacy of adjuvant chemotherapy (ACT) in elderly patients with completely resected p-stage II-IIIA non-small-cell lung cancer (NSCLC) remains unclear because all previous randomized controlled trials on ACT have been conducted among patients aged <75 years. Thus, this study aimed to evaluate the effectiveness of ACT in elderly patients with completely resected NSCLC. PATIENTS: We extracted the nationwide data of 812 patients aged ≥75 years who underwent lobectomy with mediastinal nodal dissection in 2010 and were diagnosed with p-stage II-IIIA NSCLC, from nationwide registry data accumulated in 2016. METHODS: We classified the 812 patients into 2 groups based on the ACT administration status and analyzed the differences in their postoperative overall survival (OS). RESULTS: Overall, 295 patients received ACT (36.3%; group A), whereas 517 patients did not (63.70%; group N). Group A showed significantly better OS as a whole (hazard ratio [HR]: 0.650 [95% confidence interval {CI}: 0.526-0.804]), in the p-stage II subset (HR: 0.688 [95% CI: 0.513-0.925]), and p-stage IIIA subset (HR: 0.547 [95% CI: 0.402-0.743]) than group N. Even after propensity score matching, group A showed significantly better OS as a whole (HR: 0.626 [95% CI: 0.495-0.792]), in the p-stage II subset (HR: 0.690 [95% CI: 0.493-0.964]), and p-stage IIIA subset (HR: 0.554 [95% CI: 0.398-0.772]) than group N. CONCLUSION: ACT is recommended even in elderly patients with completely resected p-stage II-IIIA NSCLC. Hence, physicians should not avoid ACT in patients with completely resected NSCLC based solely on age.

Nationwide prospective registry database of patients with newly diagnosed untreated pleural mesothelioma in Japan.

Due to the scarcity of large-sized prospective databases, the Japanese Joint Committee for Lung Cancer Registry conducted a nationwide prospective registry for newly diagnosed and untreated pleural mesothelioma. All new cases diagnosed pathologically as any subtype of pleural mesothelioma in Japan during the period between April 1, 2017, to March 31, 2019, were included before treatment. Data on survival were collected in April 2021. The eligible 346 patients (285 men [82.3%]; 61 women [17.7%]; median age, 71.0 years [range, 44-88]) were included for analysis. Among these patients, 138 (39.9%) underwent surgery, 164 (47.4%) underwent non-surgical therapy, and the remaining 44 (12.7%) underwent best supportive care. The median overall survival for all 346 patients was 19.0 months. Survival rates at 1, 2, and 3 years for all patients were, 62.8%, 42.3%, and 26.5%, respectively. Median overall survival was significantly different among patients undergoing surgery, non-surgical treatment, and best supportive care (32.2 months vs. 14.0 months vs. 3.8 months, p < 0.001). The median overall survival of patients undergoing pleurectomy/decortication and extrapleural pneumonectomy was 41.8 months and 25.0 months, respectively. Macroscopic complete resection resulted in longer overall survival than R2 resection and partial pleurectomy/exploratory thoracotomy (41.8 months vs. 32.2 months vs. 16.8 months, p < 0.001). Tumor shape, maximum tumor thickness, and sum of three level thickness were significant prognostic factors. The data in the prospective database would serve as a valuable reference for clinical practice and further studies for pleural mesothelioma.

The consecutive impact of COVID-19 on thoracic surgical procedures in Japan: an analysis of data from the National Clinical Database.

PURPOSE: The current study was designed to analyze the impact of the COVID-19 pandemic on general thoracic surgeries in Japan. METHODS: Changes in surgeries for lung cancer and metastatic lung tumors were evaluated based on National Clinical Database data regarding cancer screening. RESULTS: In 2021, surgeries for primary lung cancer increased by 3.4% compared to 2020, which, given the increase from 2014 to 2019, indicates an overall 11.1% decrease. In contrast, surgeries for metastatic lung tumors in 2021 decreased by 5.8% compared to 2020, which, given the increase from 2014 to 2020, indicates an overall 9.2% decrease. Half of the primary diseases for metastatic lung tumor were cases of colorectal cancer. Low anterior resection procedures in 2020 decreased by 5.5% compared to 2019. Lung and colon cancer screening examinees in 2021 were increased compared to 2020; however, they still showed respective decreases of 11% and 9.0% compared to 2019. CONCLUSIONS: Surgeries for primary lung cancer still decreased substantially during the COVID-19 pandemic. The continued stagnation of screening was responsible for this decrease. Surgeries for metastatic lung tumors decreased profoundly, and the decrease in screening for primary tumors was responsible for this reduction. Our findings emphasize the significance of maintaining cancer screening efforts, even during a pandemic.

Is adjuvant chemotherapy for completely resected p-stage IA (>2 cm) and stage IB non-small-cell lung cancer beneficial for elderly patients? A large, retrospective cohort study based on real-world data from Japan.

OBJECTIVE: The efficacy of tegafur-uracil as adjuvant chemotherapy for patients with completely resected stage I non-small-cell lung cancer is proven; however, its efficacy for elderly patients remains unclear. Herein, we evaluated the effectiveness of adjuvant chemotherapy for elderly patients with completely resected stage I non-small-cell lung cancer based on real-world Japanese data using propensity score matching. METHODS: This retrospective study extracted data from a nationwide registry study, performed in 2016, on patients ≥75 years who underwent lobectomy with mediastinal nodal dissection for non-small-cell lung cancer in 2010 and were diagnosed with p-stage IA (>2 cm) or stage IB non-small-cell lung cancer. We classified the 1294 patients into two groups-Group A, postoperative adjuvant chemotherapy (n = 295, 22.8%) and Group N, no adjuvant chemotherapy (n = 999, 77.2%)-and analyzed differences in postoperative overall survival between groups. RESULTS: Group A showed no advantage in overall survival over Group N as a whole (hazard ratio: 0.824 [95% confidence interval: 0.631-1.076]), in p-stage IA (hazard ratio: 0.617 [95% confidence interval: 0.330-1.156]) and in p-stage IB (hazard ratio: 0.806 [95% confidence interval: 0.597-1.088]) subsets. Even after propensity score matching, Group A showed no significant advantage in overall survival over Group N as a whole (hazard ratio: 0.975 [95% confidence interval: 0.688-1.381]), in p-stage IA (hazard ratio: 1.390 [95% confidence interval: 0.539-3.586]) and in p-stage IB (hazard ratio: 0.922 [95% confidence interval: 0.633-1.343]). CONCLUSIONS: adjuvant chemotherapy for completely resected p-stage IA (>2 cm) and stage IB non-small-cell lung cancer showed no benefit for recommendation for elderly patients; considering the risk of adverse events, we do not recommend adjuvant chemotherapy for elderly patients.

Features of anaplastic lymphoma kinase rearrangement in early-stage lung cancer: Analysis of a nationwide Japanese database.

BACKGROUND AND OBJECTIVES: Anaplastic lymphoma kinase (ALK) rearrangement is a representative driver mutation in lung cancer. However, the biology of early-stage ALK-rearranged lung cancer remains unclear. We aimed to assess the clinicopathological features, prognostic implications, and influence of ALK rearrangement on the postoperative course in surgically resected lung cancer. METHODS: We retrospectively analyzed data from the Japanese Joint Committee of Lung Cancer Registry database. Of the 12 730 patients with lung adenocarcinoma, 794 (6.2%) were tested for ALK rearrangement and were included. RESULTS: ALK rearrangements were detected in 76 patients (10%). The 5-year overall survival (OS) rate was significantly higher in the ALK rearrangement-positive group than in the ALK rearrangement-negative group (p = 0.030). Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved OS (hazard ratio, 0.521; 95% confidence interval, 0.298-0.911; p = 0.022). Regarding the postrecurrence state, there was no difference in the initial recurrence sites between both groups. Administration of ALK-tyrosine kinase inhibitors (TKIs) improved postrecurrence survival in any treatment lines. CONCLUSION: In one of the largest national surveys, ALK rearrangement was associated with improved long-term outcomes in surgically resected patients. ALK-TKIs may be an important treatment strategy for ALK rearrangement-positive lung adenocarcinoma in the postrecurrence state.

Postoperative cerebral infarction and arrhythmia after pulmonary lobectomy in Japan: a retrospective analysis of 77,060 cases in a national clinical database.

PURPOSE: To investigate the incidence of postoperative cerebral infarction after curative lobectomy, its association with the type of lobectomy, and how postoperative new-onset arrhythmia contributes to postoperative cerebral infarction. METHODS: The subjects of this analysis were 77,060 patients who underwent curative lobectomy for lung cancer between 2016 and 2018 according to the National Clinical Database. Incidences of postoperative cerebral infarction and postoperative new-onset arrhythmia were analyzed. Moreover, mediation analysis was performed to evaluate the causal pathway between postoperative new-onset arrhythmia and postoperative cerebral infarction. RESULTS: Postoperative cerebral infarction occurred in 110 (0.7%) patients after left upper lobectomy and in 85 (0.7%) patients after left lower lobectomy. Left upper lobectomy and left lower lobectomy were associated with a higher likelihood of postoperative cerebral infarction than right lower lobectomy. Left upper lobectomy was the strongest independent predictor of postoperative new-onset arrhythmia. However, in the mediation analysis, the odds ratio for cerebral infarction did not change after the addition of the factor of postoperative new-onset arrhythmia. CONCLUSION: Cerebral infarction occurred significantly more often not only after left upper lobectomy, but also after left lower lobectomy. Postoperative new-onset arrhythmia was less likely to be related to cerebral infarction after left upper lobectomy.

The efficacy of thoracoscopic surgery for descending necrotizing mediastinitis.

OBJECTIVES: Thoracotomy is a reliable approach for descending necrotizing mediastinitis (DNM), and the use of video-assisted thoracic surgery (VATS), a minimally invasive procedure, has been increasing. However, which approach is more effective for DNM treatment is controversial. METHODS: We analysed patients who underwent mediastinal drainage via VATS or thoracotomy, using a database with DNM from 2012 to 2016 in Japan, which was constructed by the Japanese Association for Chest Surgery and the Japan Broncho-esophagological Society. The primary outcome was 90-day mortality, and the adjusted risk difference between the VATS and thoracotomy groups using a regression model, which incorporated the propensity score, was estimated. RESULTS: VATS was performed on 83 patients and thoracotomy on 58 patients. Patients with a poor performance status commonly underwent VATS. Meanwhile, patients with infection extending to both the anterior and posterior lower mediastinum frequently underwent thoracotomy. Although the postoperative 90-day mortality was different between the VATS and thoracotomy groups (4.8% vs 8.6%), the adjusted risk difference was almost the same, -0.0077 with 95% confidence interval of -0.0959 to 0.0805 (P = 0.8649). Moreover, we could not find any clinical and statistical differences between the 2 groups in terms of postoperative 30-day and 1-year mortality. Although patients who underwent VATS had higher postoperative complication (53.0% vs 24.1%) and reoperation (37.9% vs 15.5%) rates than those who underwent thoracotomy, the complications were not serious and most could be treated with reoperation and intensive care. CONCLUSIONS: The outcome of DNM treatment does not depend on thoracotomy or VATS.

[Retrograde S(9+)10 Segmentectomy without Interlobar Fissurelectomy].

BACKGROUNDS: With increase of patients with a small-sized lung cancer, there is an increasing need for minimally invasive lung segmentectomy that can preserve respiratory function. We perform S(9+)10 segmentectomy with retrograde dissection of the pulmonary vein, bronchus, pulmonary artery, in order, without interlober fissurelectomy and staple dissection of the peripheral lung parenchyma. METHODS: Seven patients who underwent retrograde S(9+)10 segmentectomy between June, 2021 and May, 2022 in our hospital were retrospectively reviewed. RESULTS: No patient was converted to the open thoracotomy, without any complications including prolonged air leakage. The average operation time was 171 minutes( range 125 to 221), amount of bleeding was 25 ml( range 0 to 75). Median duration of chest tube insertion was 4 days( range 3 to 6), length of stay after surgery was 6 days (range 5 to 9). Pathologic stage showed pT1mi in 3 patients, pT1a in 3 patients, pT2a in 1 patient. No local recurrence was seen at this time. CONCLUSIONS: Retrograde S(9+)10 segmentectomy is feasible and facilitates interlobar procedure at the time of repeated segmentectomy or completion lobectomy.

Do blood flow patterns in the left atriums differ between left upper lobectomy and other lobectomies? A computational study.

Background: Left atrial (LA) hemodynamics after lung lobectomies with pulmonary vein (PV) resection is widely understood to be a risk factor for LA thrombosis. A recent magnetic resonance imaging study showed that left upper lobectomy (LUL) with left superior pulmonary vein resection tended to cause LA flow patterns distinct from those of other lobectomies, with flow disturbances seen near the PV stump. However, little is known about this flow pattern because of severe image resolution limitations. The present study compared flow patterns in the LA after LUL with the flow patterns of other lobectomies using computational simulations. Methods: The computational simulations of LA blood flow were conducted on the basis of four-dimensional computed tomography images of four lung cancer patients prior to lobectomies. Four kinds of PV resection cases were constructed by cutting each one of the PVs from the LA of each patient. We performed a total of five cases (pre-resection case and four PV resection cases) in each patient and evaluated global flow patterns formed by the remaining PV inflow, especially in the upper LA region. Results: LUL tended to enhance the remaining left inferior PV inflow, with impingements seen in the right PV inflows in the upper LA region near the PV stump. These flow alterations induced viscous dissipation and the LUL cases had the highest values compared to other PV resection cases, especially in the LV systole in three patients, and reached three to four times higher than those in pre-resection cases. However, in another patient, these tendencies were weaker when PV inflow was stronger from the right side than from the left side, and the degree of flow dissipation was lower than those in other PV resection cases. Conclusion: These findings suggest marked variations in LA flow patterns among patients after lobectomies and highlights the importance of patient-specific assessment of LA hemodynamics after lobectomies.

Hazard Function Analysis of Recurrence in Patients with Curatively Resected Lung Cancer: Results from the Japanese Lung Cancer Registry in 2010.

To optimize postoperative surveillance of lung cancer patients, we investigated the hazard function of tumor recurrence in patients with completely resected lung cancer. We analyzed the records of 12,897 patients in the 2010 Japanese Joint Committee of Lung Cancer Registry who underwent lobectomy to completely resect pathological stage I-III lung cancer. The risk of postoperative recurrence was determined using a cause-specific hazard function. The hazard function for recurrence exhibited a peak at approximately 9 months after surgery, followed by a tapered plateau-like tail extending to 60 months. The peak risk for intrathoracic recurrence was approximately two-fold higher compared with that of extrathoracic recurrence. Subgroup analysis showed that patients with stage IIIA adenocarcinoma had a continuously higher risk of recurrence compared with patients with earlier-stage disease. However, the risk of recurrence in patients with squamous cell carcinoma was not significantly different compared with that more than 24 months after surgery, regardless of pathological stage. In conclusion, the characteristics of postoperative tumor recurrence hazard in a large cohort of lung cancer patients may be useful for determining the time after surgery at which patients are at the highest risk of tumor recurrence. This information may improve stage-related management of postoperative surveillance.

The impact of COVID-19 on thoracic surgical procedures in Japan: Analysis of data from the National Clinical Database.

OBJECTIVE: The COVID-19 pandemic has far-reaching collateral health impacts on the ongoing delivery of surgical care worldwide. The current study was designed to analyze the impact of the COVID-19 pandemic on the number of surgeries of general thoracic surgery in Japan. METHODS: Changes in the number of surgeries for total and three representative tumors were analyzed using the National Clinical Database data with reference to the pandemic infection rate and lung cancer screening. RESULTS: In 2020, the number of surgeries in total and for primary lung cancer and mediastinal lung tumor decreased by 4.9, 5.1, and 5.0 %, respectively. Considering the five-year trend towards a 5 % annual increase, there was a potential 10 % decrease in the number of primary lung cancer surgeries. The number of primary lung cancer surgeries bottomed in July 2020 but recovered towards the end of the year. In contrast, the number of metastatic lung tumor surgeries in 2020 increased by 3.2 %, following a similar trend observed over the previous five years. The number of lung cancer screening examinees decreased markedly with the lowest number in May. Our findings indicate that surgical triage had a limited impact on the decrease in primary lung cancer surgeries during the pandemic; rather, the decrease in lung cancer screening, which was a few months preceding, is most likely responsible. CONCLUSIONS: The decrease in primary lung cancer was mainly caused by the decrease in lung cancer screening, indicating that continuing screening is vital even during a pandemic.

The prognostic impact of lung adenocarcinoma predominance classification relating to pathological factors in lobectomy, the Japanese Joint Committee of Lung Cancer Registry Database in 2010.

OBJECTIVE: We studied the prognosis and clinicopathological background of lung adenocarcinoma predominance among patients who underwent lobectomy using data from the Japanese Joint Committee of Lung Cancer Registry. METHODS: Two thousand eight hundred sixty-three cases were extracted. Recurrence free survival (RFS) rates, overall survival (OS) rates and clinicopathological factors and epidermal growth factor receptor (EGFR) mutation status were examined. RESULTS: Median follow-up period was 65.5 months. Adenocarcinoma predominance was sub-grouped according to OS and RFS rate. In pathological stage I, 5-year RFS and OS rates were respectively 92.2% and 95.8% in group A (adenocarcinoma-in-situ + minimally invasive adenocarcinoma), 89.3% and 92.1% in group B (lepidic), 79.2% and 89.7% in group C (papillary + acinar + variants) and 69.0% and 79.0% in group D (solid + micropapillary). In pathological stage II + IIIA, they were, 43.6% and 72.4% in B, 39.5% and 66.9% in C and 31.0% and 53.7% in D. Group D showed significant worst outcome both in stage I and II + IIIA. Up stage rate from clinical stage I to pathological stage II + IIIA was 0.0%, 3.7%, 15.9% and 33.3%. The frequency of lymph-vessel, vascular, pleura invasion and positive EGFR mutation were 0.0%, 0.0%, 0.0% and 57.1% in group A, 15.6%, 10.0%, 12.1% and 55.1% in B, 36.6%, 31.8%, 29.7% and 44.9% in C, 50.2%, 57.8%, 38.9% and 21.3% in D. In group D, lymph-vessel, vascular and pleura invasion were most, EGFR mutation was least frequent not only in pathological stage I but also stage II + IIIA. In multivariate analysis, age, pathological stage, vascular invasion, and group D were independent factors affected RFS and OS. CONCLUSION: Limited to lobectomy cases, solid + micropapillary was independent prognostic factor both in early and locally advanced stage. Its malignant degree was related to the frequency of pathological invasive factors and EGFR mutation status.