Papillary Predominant Subtype Research Articles

Prognostic value of predominant subtype in pathological stage II–III lung adenocarcinoma with epidermal growth factor receptor mutation

ObjectivesThis study extracted clinicopathological features associated with recurrence and evaluated the tumor microenvironment in consecutive cases with resected pathological stage II–III epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (EGFR-mt). MethodsBetween January 2008 and November 2018, we retrospectively reviewed 387 consecutive patients with pathological stage II–III lung adenocarcinoma who underwent surgical resection. We examined the EGFR mutation status (wild-type or mutant) and the evaluated clinicopathological features of all patients. In addition, tumor-promoting cancer-associated fibroblasts (CAFs), tumor-associated M2 macrophages (TAMs), and tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment of EGFR-mt cells were evaluated by immunohistochemical analysis. ResultsEGFR-mt (n = 124, 32 %) had more lymph node and pulmonary metastases than EGFR-wild-type lung adenocarcinoma (EGFR-wt) despite the smaller invasive component size. The disease-free survival (DFS) of patients with EGFR-mt tended to be shorter than that of patients with EGFR-wt. In the analysis according to the predominant subtype, EGFR-mt with papillary-predominant subtype had a significantly shorter 5-year DFS than that of EGFR-wt with papillary-predominant subtype (15.3 % vs. 44.1 %, p < 0.01). We observed no significant differences among the other subtypes. Multivariate analysis of DFS in patients with EGFR-mt revealed that male sex, pathological stage III, lymph node metastasis, pulmonary metastasis in the same lobe and non-acinar and non-lepidic predominant subtypes (papillary, solid, or micropapillary) were independent poor prognostic factors. Immunohistochemical analysis of EGFR-mt revealed that non-acinar- and non-lepidic-predominant subtypes were associated with a higher frequency of podoplanin-positive CAFs (36 % vs. 13 %, p = 0.01) and a higher median number of CD204-positive TAMs (61 vs. 49, p = 0.07) compared to the acinar- or lepidic-predominant subtypes. ConclusionsNon-acinar and non-lepidic predominant subtypes were predictors of recurrence and had an aggressive tumor microenvironment in pathological stage II–III EGFR-mt.

The correlation between metabolic parameters in (18)F-FDG PET-CT and solid and micropapillary histological subtypes in lung adenocarcinoma

Objective: Solid and micropapillary pattern are highly invasive histologic subtypes in lung adenocarcinoma and are associated with poor prognosis while the biopsy sample is not enough for the accurate histological diagnosis. This study aims to assess the correlation and predictive efficacy between metabolic parameters in (18)F-fluorodeoxy glucose positron emission tomography/computed tomography ((18)F-FDG PET-CT), including the maximum SUV (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and solid and micropapillary histological subtypes in lung adenocarcinoma. Methods: A total of 145 resected lung adenocarcinomas were included. The clinical data and preoperative (18)F-FDG PET-CT data were retrospectively analyzed. Mann-Whitney U test was used for the comparison of the metabolic parameters between solid and micropapillary subtype group and other subtypes group. Receiver operating characteristic (ROC) curve and areas under curve (AUC) were used for evaluating the prediction efficacy of metabolic parameters for solid or micropapillary patterns. Univariate and multivariate analyses were conducted to determine the prediction factors of the presence of solid or micropapillary subtypes. Results: Median SUV(max) and TLG in solid and papillary predominant subtypes group (15.07 and 34.98, respectively) were significantly higher than those in other subtypes predominant group (6.03 and 10.16, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for prediction of solid and micropapillary predominant subtypes [AUC=0.811(95% CI: 0.715~0.907) and 0.725(95% CI: 0.610~0.840), P<0.05]. Median SUV(max) and TLG in lung adenocarcinoma with the solid or micropapillary patterns (11.58 and 22.81, respectively) were significantly higher than those in tumors without solid and micropapillary patterns (4.27 and 6.33, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for predicting the presence of solid or micropapillary patterns [AUC=0.757(95% CI: 0.679~0.834) and 0.681(95% CI: 0.595~0.768), P<0.005]. Multivariate logistic analysis showed that the clinical stage (Stage Ⅲ-Ⅳ), SUV(max) ≥10.27 and TLG≥7.12 were the independent predictive factors of the presence of solid or micropapillary patterns (P<0.05). Conclusions: Preoperative SUV(max) and TLG of lung adenocarcinoma have good prediction efficacy for the presence of solid or micropapillary patterns, especially for the solid and micropapillary predominant subtypes and are independent factors of the presence of solid or micropapillary patterns.

Volume and Mass Doubling Time of Lung Adenocarcinoma according to WHO Histologic Classification.

ObjectiveThis study aimed to evaluate the tumor doubling time of invasive lung adenocarcinoma according to the International Association of the Study for Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic classification.Materials and MethodsAmong the 2905 patients with surgically resected lung adenocarcinoma, we retrospectively included 172 patients (mean age, 65.6 ± 9.0 years) who had paired thin-section non-contrast chest computed tomography (CT) scans at least 84 days apart with the same CT parameters, along with 10 patients with squamous cell carcinoma (mean age, 70.9 ± 7.4 years) for comparison. Three-dimensional semiautomatic segmentation of nodules was performed to calculate the volume doubling time (VDT), mass doubling time (MDT), and specific growth rate (SGR) of volume and mass. Multivariate linear regression, one-way analysis of variance, and receiver operating characteristic curve analyses were performed.ResultsThe median VDT and MDT of lung cancers were as follows: acinar, 603.2 and 639.5 days; lepidic, 1140.6 and 970.1 days; solid/micropapillary, 232.7 and 221.8 days; papillary, 599.0 and 624.3 days; invasive mucinous, 440.7 and 438.2 days; and squamous cell carcinoma, 149.1 and 146.1 days, respectively. The adjusted SGR of volume and mass of the solid-/micropapillary-predominant subtypes were significantly shorter than those of the acinar-, lepidic-, and papillary-predominant subtypes. The histologic subtype was independently associated with tumor doubling time. A VDT of 465.2 days and an MDT of 437.5 days yielded areas under the curve of 0.791 and 0.795, respectively, for distinguishing solid-/micropapillary-predominant subtypes from other subtypes of lung adenocarcinoma.ConclusionThe tumor doubling time of invasive lung adenocarcinoma differed according to the IASCL/ATS/ERS histologic classification.

Papillary predominant histological subtype predicts poor survival in lung adenocarcinoma.

This study aims to investigate whether papillary predominant histological subtype can predict poor survival in lung adenocarcinoma. Between January 2005 and December 2016, a total of 80 patients with papillary predominant subtype lung adenocarcinoma (70 males, 10 females; mean age 60.7 years; range, 42 to 79 years) operated in our clinic were included in the study. These patients were compared with those having lepidic, acinar, and mucinous subtypes. Overall and five-year survival rates were evaluated. Five-year survival was 40.5% in papillary predominant histological subtype, while this rate was 70.9%, 59.0%, and 66.6% in lepidic, acinar, and mucinous subtypes, respectively. Papillary subtype showed significantly poor survival compared to lepidic (p=0.002), acinar (p=0.008), and mucinous subtypes (p=0.048). In Stage 1 disease, it was more evident (papillary, 47.5%, lepidic 86.9% [p=0.001], acinar 69.3% [p=0.040], and mucinous 90.0% [p=0.050]). Our study results suggest that papillary predominant subtype predicts poor survival in lung adenocarcinoma and these cases may be candidates for adjuvant treatment modalities even in the earlier stages of disease.

The lymph node status and histologic subtypes influenced the effect of postoperative radiotherapy on patients with N2 positive IIIA non-small cell lung cancer.

To investigate the role of postoperative radiotherapy (PORT) in IIIA-N2 non-small cell lung cancer (NSCLC) patients and subgroups which derived benefit from PORT. A total of 576 patients with pathological IIIA-N2 NSCLC, who underwent complete resection, were identified. Propensity score matching (PSM) methods were used to balance the patients'characteristics between two groups. Overall survival (OS) and relapse-free survival (RFS) were compared between PORT and non-PORT patients. On multivariable analysis, improved OS remained correlated with younger age, single N2 station involvement, less positive lymph nodes, and chemotherapy. After PSM, 121 PROT patients and 242 non-PORT patients were matched. PORT was not associated improved patients' OS (P = 0.735) or RFS ( P = 0.483). For patients who underwent postoperative chemotherapy (POCT), PORT could improve OS in single N2 station involved patients (HR: 0.572, 95%CI: 0.312 to 1.05, P = 0.040). Patients with papillary predominant adenocarcinoma also benefited from PORT with an increase in OS (HR: 0.350, 95%CI: 0.126 to 0.972, P = 0.033). For patients with completely resected IIIA-N2 NSCLC, mediastinal lymph node metastasis and histologic subtypes could influence the effect of PORT. Single N2 station involvement and papillary predominant subtype were predictors of benefit from PORT.

Prognostic value of epidermal growth factor receptor mutations and histologic subtypes with lung adenocarcinoma.

The epidermal growth factor receptor (EGFR) mutation status has become one of the most important factors in the treatment of non-small cell lung cancer. However, the relationship between EGFR mutation and the histologic subtype of lung adenocarcinoma remains to be fully elucidated. We examined the relationship between the predominant subtype of adenocarcinoma and the prognosis and investigated the correlation between a new subtype of adenocarcinoma and EGFR mutations. This study included 182 patients with adenocarcinoma who underwent complete resection. The rate of EGFR mutation-positive patients was significantly higher among female patients, never smokers, patients with small tumors (<3cm in size), patients with well-differentiated tumors, and patients with a pStage I classification. The rates of adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic-predominant subtype were high in male EGFR mutation-positive patients. The prevalence of the acinar and papillary-predominant subtypes was high among EGFR mutation-positive female patients, as was AIS, MIA, and the lepidic-predominant subtype. The progression-free survival (PFS) of the EGFR mutation-positive patients was significantly better than that of the EGFR mutation-negative patients (75.8 vs 67.1%, p=0.03). However, the multivariate analysis of clinicopathologic and histologic factors did not reveal the prognostic impact of the EGFR mutation status on PFS. The overall survival (OS) of the EGFR mutation-positive patients was significantly better than that of the EGFR mutation-negative patients (93.7 vs 63.4%, p<0.01). However, in the multivariate analysis the EGFR mutation status was not significantly associated with OS.

Epidemiological study of HER-2 mutations among EGFR wild-type lung adenocarcinoma patients in China.

Background Human epidermal growth factor receptor (HER)-2 is a driver gene in non-small cell lung cancer (NSCLC). The present study evaluated the mutation rate of HER-2 within the wild-type epidermal growth factor receptor (EGFR) lung adenocarcinoma population in China.MethodsFormalin-fixed, paraffin-embedded samples from 456 patients with wild-type EGFR lung adenocarcinoma were analyzed for HER-2 mutations by amplification-refractory mutation system (ARMS), and HER-2 protein expression was evaluated by immunohistochemistry. All samples positive for HER-2 mutation underwent direct sequencing for further verification.Results HER-2 mutation was detected in 22/456 cases (4.8 %); the rate was 6.7 % among 331 triple-negative samples (i.e., wild-type EGFR, anaplastic lymphoma kinase, and ROS proto-oncogene 1). Direct sequencing confirmed that the results were consistent with those obtained by ARMS analysis in 19 cases. The positive rate was 15.4 % by immunohistochemical analysis of HER-2 expression; this was not correlated with mutation rate. HER-2 mutation and positivity were not correlated with gender, age, smoking status, disease stage, or histological subtype. The 22 cases of HER-2 mutations occurred only in acinar (36.4 %), papillary (36.4 %), minimally invasive (13.6 %), solid (9.2 %), and invasive mucinous (4.5 %) subtypes. Disease-free and overall survival were not associated with HER-2 mutation or HER-2 protein overexpression.ConclusionThe HER-2 mutation rate was 4.8 % among EGFR wild-type lung adenocarcinoma patients in China, and 6.7 % among driver genes, triple-negative lung adenocarcinoma. The incidence of HER-2 mutation varied among different lung adenocarcinoma subtypes, occurring mainly in acinar and papillary predominant subtypes. 15.4 % of EGFR wild-type lung adenocarcinoma patients showed HER-2 protein overexpression, but this was not correlated to HER-2 mutation. Existing follow-up data did not show a correlation between HER-2 mutation with DFS or OS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2875-z) contains supplementary material, which is available to authorized users.

Expression of epidermal growth factor receptor mutation specific antibodies in lung adenocarcinoma: evaluation of sensitivity, specificity and relationship to histologic subtypes

To evaluate the expression of epidermal growth factor receptor (EGFR) mutation specific antibodies in invasive lung adenocarcinomas, and their sensitivity, specificity, as well as relationship to histological subtypes. Immunostaining with EGFR mutation-specific antibodies, del E746-A750 in exon 19 and L858R in exon 21, was performed in tissue microarrays of 884 cases of resection specimens to study the relationship between the immunophenotypes and morphologic subtypes. The sensitivity and specificity of the stains were compared with gene mutations detected by amplified refractory mutation system-polymerase chain reaction (ARMS-PCR). Of the 884 cases, the expression of del E746-A750 in exon 19 was 3+ , 2+ , 1+ and 0 in 7 cases (0.79%), 38 cases (4.30%), 129 cases (14.59%) and 710 cases (80.32%), respectively. For L858R in exon 21, 3+ , 2+ , 1+ and 0 staining were seen in 82 cases (9.28%), 93 cases (10.52%), 82 cases (9.28%) and 627 cases (70.93%), respectively. For both antibodies, positive expression (1+ or more) was mainly observed in lepidic, acinar and papillary predominant subtypes, and rarely seen in solid subtype or invasive mucinous adenocarcinoma (P=0.014 and 0.016). If 1+ to 3+ expression was set as positive, the specificity of exon 19/exon 21 reached 98.59%/92.98%, while the sensitivity was relatively lower (62.86%/88.89%). If 2+ to 3+ expression was read as positive, the specificity and sensitivity were 99.30%/97.37% and 25.71%/74.60% for exon 19/exon 21. If only 3+ expression was considered positive, the specificity was 100.0% for both antibodies, with a low sensitivity (8.57% for exon 19 and 34.92% for exon 21). Of the 18 cases with E746-A750 del in exon 19 based on molecular detection, the sensitivity of immunohistochemistry for exon 19 was 88.89% if a positive cutoff value ≥1+ was used; in contrast, of the 8 cases harboring other deletions in exon 19, only two cases were positive as 1+ . Both the EGFR mutation specific antibodies del E746-A750 in exon 19 and L858R in exon 21 demonstrate high specificity and relatively low sensitivity, and are mostly expressed in lepidic, acinar and papillary predominant subtypes, but rarely in solid subtype or invasive mucinous adenocarcinoma. For cases with 3+ expression, a mutational statue for EGFR is likely. For the 2+ positive cases, the accuracy to predict mutation almost reaches 90%, but molecular detection for confirmation is desirable. For the 1+ and negative cases, DNA-based test is essential to avoid false negativity.

Prognostic value of MMP9 activity level in resected stage I B lung adenocarcinoma.

The clinical outcomes of patients with early‐stage non‐small cell lung cancer (NSCLC) have remained unsatisfactory after complete surgical resection. The objective of this study was to explore the prognostic value of matrix metalloproteinase 9 (MMP9) activity level in Chinese patients with stage I B lung adenocarcinoma. A sensitive and validated method was employed for determining the activity of MMP9 in human lung adenocarcinoma cells in vitro. Then, the association was examined between the level of MMP9 enzymatic activity and clinical outcomes. A total of 104 cases were stratified according to the IASLC/ATS/ERS classification scheme and activity of MMP9 was analyzed by SensoLyte® assay kit. The results showed that the MMP9 activity was the highest in solid predominant and micropapillary predominant subtypes, intermediate in acinar predominant and papillary predominant subtypes, and the lowest in lepidic predominant subtype. Multivariate analysis revealed that pathological subtype and activity of MMP9 were independent prognostic factors for disease‐free survival (DFS), respectively (P = 0.005 and 0.029). Significant relationship existed between enzyme activity of MMP9 and prognosis. And the 30 months DFS of high‐ and low‐level MMP9 activity tumors was 44.2% and 84.1% (P < 0.0001), respectively. High‐level MMP9 activity is correlated with aggressive tumor behaviors and poor clinical outcomes in early‐stage lung adenocarcinoma after complete resection.

Association between the histological subtype of lung adenocarcinoma, EGFR/KRAS mutation status and the ALK rearrangement according to the novel IASLC/ATS/ERS classification.

The present study aimed to investigate the association between epidermal growth factor receptor (EGFR)/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements and the morphological characteristics of lung adenocarcinoma (LAC), according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification in a large group of patients with primary LAC. A total of 200 patients with invasive LAC who had undergone complete resections at the Beijing Chest Hospital (Beijing, China) were randomly selected. The morphology of the samples was reassessed in 5% increments by two pathologists, according to the IASLC/ATS/ERS scheme. EGFR and KRAS mutations were tested by direct DNA sequencing. ALK rearrangements were screened by immunohistochemistry on a Benchmark XT stainer. The data revealed that EGFR and KRAS mutations, and ALK rearrangements were identified in 46.0% (92/200), 9.0% (18/200) and 11.5% (23/200) of the patients, respectively. The EGFR/KRAS mutations and ALK rearrangements were mostly exclusive. However, 1 patient exhibited the coexistence of the EGFR (at exon 20) and KRAS (codon 12) mutations, and another patient exhibited the coexistence of the EGFR mutation (at exon 21) and the ALK gene fusion. EGFR mutations were indicated to be closely associated with the acinar predominant (43/77; 55.8%; P=0.030) and papillary predominant (26/49; 53.1%; P=0.006) subtypes. KRAS mutations were more commonly associated with the solid predominant subtype (9/52; 17.3%; P=0.023) and invasive mucinous LAC (5/10; 50.0%; P=0.004), and less commonly associated with the acinar predominant subtype (1/77; 1.3%; P=0.002). ALK rearrangements more commonly occurred in the solid predominant subtype compared with other subtypes (13/52; 25%; P=0.002), and less commonly occurred in the papillary predominant subtype (1/49; 2.0%; P=0.004). Tumors harboring ALK rearrangements were characterized by signet-ring cell (7/9; 77.8%; P<0.0001) and cribriform (7/12; 58.3%; P<0.0001) patterns. The association between the mutation status and histological subtype in LAC was distinct. The predominant subtype according to the IASLC/ATS/ERS classification provided important information for gene mutations and integrated clinical findings to improve the treatment of LAC patients.

Negative prognostic influence of micropapillary pattern in stage IA lung adenocarcinoma.

There is uncertainty as to which factors determine the aggressiveness of lung adenocarcinoma with a micropapillary pattern (MPP). The present study aimed to clarify the influence of a MPP on the malignant aggressiveness of clinical stage IA lung adenocarcinoma. We retrospectively examined 347 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection. We defined MPP-positive as accounting for ≥5% of the entire tumour. Forty-eight (14%) and 299 (86%) patients were MPP-positive and negative, respectively. Lymphatic (P = 0.003) and vessel (P = 0.029) invasion as well as lymph node metastasis (P = 0.002) were more frequent in the MPP-positive than negative group. Five-year disease-free survival (DFS) rates were significantly lower in the MPP-positive than negative group (69.7 vs 89.3%, P < 0.001). Multivariate analysis for DFS showed that MPP (P = 0.048), lymphatic invasion (P = 0.003) and vessel invasion (P = 0.002) were independent poor prognostic factors. In addition, higher proportions (<5%, 5-30% and ≥30%) of MPP were associated with a poorer prognosis (89.3, 76.0, and 48.1%, respectively; P < 0.001). The prognosis of patients with MPP-positive tumours and negative tumours harbouring lepidic and solid predominant growth patents did not differ (100 vs 96.8%, P = 0.564; 66.7 vs 62.5%, P = 0.791, respectively). On the other hand, the prognosis tended to be poorer for patients with papillary predominant MPP-positive tumours than for those with negative tumours (62.5 vs 82.5%, P = 0.075). MPP has an effect on tumour malignancy and patients with tumours harbouring a higher ratio of MPP or papillary predominant subtypes have worse survival.

ALK gene fusion associated non-small cell lung cancer: automated immunostainer detection and clinicopathologic perspectives

To explore the automated immunostainer screening anaplastic lymphoma kinase (ALK) gene fusion non-small cell lung cancer (NSCLC) and clinicopathological characteristics of the molecular subtype lung cancers. Methods Five hundred and sixty-six cases of NSCLC were collected over a 16 month period. The test for ALK was performed by Ventana automated immunostainer with anti-ALK D5F3. The histological features, treatment and outcome of patients were assessed. Results Thirty-eight cases (6.7%, 38/566) of NSCLC showed ALK gene fusion. The frequency of ALK gene fusion was higher in male (7.1%, 25/350) than that in female (6.0%, 13/216) patients, but not achieving statistical significance (chi2 = 0.270, P = 0.604). ALK + NSCLC was more significantly more frequent in patients < or = 60 years (9.9%, 28/282) than >60 years (3.5% , 10/284) of age. Histologically, the ALK + NSCLCs were mostly adenocarcinoma (81.6%, 31/38) , among which eighteen cases were solid predominant subtype with mucin production; nine cases were acinar predominant subtype; one case was papillary predominant subtype and three cases were invasive mucinous adenocarcinoma. The ALK + non-adenocarcinoma included three cases of squamous cell carcinoma, three cases of adenosquamous carcinoma and one case of pleomorphic carcinoma. Among the ALK + NSCLC patients, the number of non/light cigarette smokers (86. 8% , 33/38) was more than that of heavy smokers. Twenty-nine cases were stages III and IV; twenty-nine cases showed lymph node metastasis; twenty cases showed metastases mostly to brain and bone; and one case showed EGFR gene mutation coexisting with ALK gene fusion. Twelve of fifteen patients received crizotinib therapy and remained stable. Conclusions NSCLC with ALK gene rearrangement shows distinctive clinical and histological features. Ventana-IHC may he a feasible and valid technique for detection of ALK rearrangement in NSCLC.

Tumor-size-based morphological features of metastatic lymph node tumors from primary lung adenocarcinoma.

Most primary lung adenocarcinomas show histological diversity, however, histological diversity in the metastatic lymph node tumors (LNT) is not well defined. The aim of this study was to explore the histological characteristics of the metastatic LNT based on their sizes. We analyzed 163 primary tumors and 509 metastatic LNTs. When the primary tumor showed papillary-predominant subtype, the most frequent histological subtype in the metastatic LNT that were ≤2 mm in diameter was solid subtype (49%), followed by papillary subtype (35%); on the other hand, in the metastatic LNT measuring >2 mm in size, the frequency of tumors showing papillary-predominant subtype increased significantly to 52% (P = 0.04). When the primary tumor showed acinar-predominant subtype, the most predominant subtype in the ≤2 mm metastatic LN tumors was acinar subtype (55%), followed by solid subtype (40%), with the frequency of acinar subtype increasing significantly to 76% in the metastatic LNT that were >2 mm in diameter (P = 0.04). These results indicate that solid subtype is the characteristic histological subtype in the early phase of the LN metastatic process, and that as the metastatic LNT grow larger, they develop morphological features resembling those in the primary tumor.

Expression Profiles and Clinicopathologic Features in Early Resected Non-small-cell Lung Cancer

Expression Profiles and Clinicopathologic Features in Early Resected Non-small-cell Lung Cancer

Risk factors of recurrence for resected T1aN0M0 invasive lung adenocarcinoma: a clinicopathologic study of 177 patients.

BackgroundThis study aimed at identifying risk factors of recurrence for completely resected pathologic T1aN0M0 lung adenocarcinomas.MethodsWe reviewed the records of 177 T1aN0M0 invasive adenocarcinoma patients, and re-classified achieved surgical specimens according to the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification. Impact on recurrence-free survival (RFS) for age, gender, smoking history, lymphovascular invasion (LVI) and new classification was analyzed by log-rank test and Cox regression. Two existing prognostic grouping schemes of new classification were compared, and subsequently, the correlation of high-grade group in the better prognostic grouping model with clinical data was investigated statistically.ResultsThe 5-year recurrence-free rate was 83.7%. The LVI and new adenocarcinoma classification were significantly associated with 5-year RFS (P = 0.012; P = 0.022, respectively). The designation of papillary predominant subtype in the low-grade group, along with lepidic- and acinar predominant subtype had more prognostic significance than the model of combining papillary-, solid- and micropapillary predominant subtypes as the high-grade group (P = 0.005 versus P = 0.181). This high-grade group has increased risk of recurrence in a multivariate Cox regression (adjusted HR 2.815, 95% CI: 1.239 to 6.397, P = 0.013), and is associated significantly more with male gender (adjusted OR 2.214, 95% CI: 1.050 to 4.668, P = 0.037), and, with borderline significance, the presence of LVI (adjusted OR 2.091, 95% CI: 0.938 to 4.662, P = 0.071).ConclusionsOur results showed that the solid- and micropapillary predominant subtype of IASLC/ATS/ERS classification remains the only risk factor for post-operative recurrence of T1aN0M0 adenocarcinomas, suggesting that they can be indicators of aggressive tumor behaviors.