Effect of Resected Lung Volume on Pulmonary Function and Residual Lung Volume in Patients Undergoing Segmentectomy: A Retrospective Study.

PURPOSE: We elucidated the effects of planned resection volume on postoperative pulmonary function and changes in residual lung volume during segmentectomy. METHODS: This study included patients who underwent thoracoscopic segmentectomy between January 2017 and December 2022 and met eligibility criteria. Pre- and post-resection spirometry and computed tomography were performed. Three-dimensional reconstructions were performed by using computed tomography images to calculate the volumes of the resected, remaining, and nonoperative side regions. Based on the resected region volume, patients were divided into the higher and lower volume segmentectomy groups. Changes in lung volume and pulmonary function before and after the surgery were comparatively analyzed. RESULTS: The median percentage of resected lung volume was 10.9%, forming the basis for categorizing patients into the two groups. Postoperative forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) ratios to preoperative measurements in both groups did not differ significantly (FEV1, p = 0.254; FVC, p = 0.777). Postoperative FEV1 and FVC ratios to their predicted postoperative values were significantly higher in the higher volume segmentectomy group than in the lower volume segmentectomy group (FEV1, p = 0003; FVC, p < 0.001). The higher volume segmentectomy group showed significantly greater post-to-preoperative lung volume ratio in overall, contralateral, ipsilateral, residual lobe and residual segment than the lower volume segmentectomy group. CONCLUSIONS: Postoperative respiratory function did not differ significantly between the higher- and lower-volume segmentectomy groups, indicating improved respiratory function because of substantial postoperative residual lung expansion. Our findings would aid in determining the extent of resection during segmentectomy.

A randomized phase III trial of postoperative surveillance for pathological stage II and IIIA non-small cell lung cancer (JCOG2012, PHOENIX).

The goal of postoperative surveillance following non-small cell lung cancer surgery is to detect recurrence and second primary malignancies while curative treatment is still possible. Although several guidelines recommend that patients have computed tomography (CT) scans every 6 months for the first 2 years after resection, then once a year, there is no evidence that it is effective for survival, especially in locally advanced non-small cell lung cancer. In October 2022, we launched a multi-institutional, randomized controlled phase III trial for pathological stage II and IIIA non-small cell lung cancer patients to confirm the non-inferiority of less intensive surveillance with less frequent CT scans versus standard surveillance in terms of overall survival. The primary endpoint is overall survival. We intend to enroll 1100 patients from 45 institutions over 4 years. The trial has been registered in the Japan Registry of Clinical Trials under the code jRCT1030220361 (https://jrct.niph.go.jp/latest-detail/jRCT1030220361).

Ten-year follow-up outcomes of limited resection trial for radiologically less-invasive lung cancer.

BACKGROUND: The JCOG0804/WJOG4507L single-arm confirmatory trial indicated a satisfactory 10-year prognosis for patients who underwent limited resection for radiologically less-invasive lung cancer. However, only one prospective trial has reported a 10-year prognosis. METHODS: We conducted a multicenter prospective study coordinated by the National Cancer Center Hospital East and Kanagawa Cancer Center. We analyzed the long-term prognosis of 100 patients who underwent limited resection of a radiologically less-invasive lung cancer in the peripheral lung field. We defined radiologically less-invasive lung cancer as lung adenocarcinoma with a maximum tumor diameter of ≤2 cm, tumor disappearance ratio of ≥0.5 and cN0. The primary endpoint was the 10-year local recurrence-free survival. RESULTS: Our patients, with a median age of 62 years, included 39 males. A total of 58 patients were non-smokers; 87 had undergone wide wedge resection and 9 underwent segmentectomy. A total of four cases were converted to lobectomy because of the presence of poorly differentiated components in the frozen specimen or insufficient margin with segmentectomy. The median follow-up duration was 120.9 months. The 10-year recurrence-free survival and overall survival rates of patients with lung cancer were both 96.0%. Following the 10-year long-term follow-up, two patients experienced recurrences at resection ends after wedge resection. CONCLUSIONS: Limited resection imparted a satisfactory prognosis for patients with radiologically less-invasive lung cancer, except two cases of local recurrence >5 years after surgery. These findings suggest that patients with this condition who underwent limited resection may require continued follow-up >5 years after surgery.

EGFR mutation impacts recurrence in high-risk early-stage lung adenocarcinoma in the IASLC grading system.

INTRODUCTION: The developments of perioperative treatments for patients with high-risk early-stage lung cancer are ongoing, however, real-world data and evidence of clinical significance of genetic aberration are lacking in this population. This study aimed to identify patients with early-stage lung adenocarcinoma at high risk for recurrence based on pathological indicators of poor prognosis, including the International Association for the Study of Lung Cancer (IASLC) grade, and elucidate the prognostic impact of epidermal growth factor receptor mutation (EGFRm) status. METHODS: This retrospective study included 494 consecutive patients who underwent complete resection for pathological stage I lung adenocarcinoma between 2011 and 2016. The patients were evaluated for EGFRm and IASLC grade. Multivariable analysis was used to identify pathological factors for poor prognosis associated with recurrence-free survival (RFS) and overall survival (OS). Patients with any one of these factors were classified into the high-risk group. The prognostic impact of EGFRm was evaluated using RFS, OS, and cumulative recurrence proportion. RESULTS: Multivariable analysis for RFS and OS revealed that IASLC grade 3, pathological invasion size>2 cm, and presence of lymphovascular invasion were indicators of poor prognosis. EGFRm-positive patients had a higher incidence of all types of recurrence, including central nervous system (CNS) metastasis and distant metastasis in high-risk group, but not in low-risk group. CONCLUSIONS: This study provides evidence that patients with EGFRm-positive stage I lung adenocarcinoma in the high-risk group have an increased risk of recurrence, including CNS metastasis. These findings highlight the need for development of adjuvant treatment in this population.

Long-term outcomes of 5-year survivors without recurrence after the complete resection of non-small cell lung cancer after lobectomy: a landmark analysis in consideration of competing risks.

PURPOSE: Among non-small cell lung cancers (NSCLC), 5 years is a benchmark in cancer control and treatment, but a certain percentage of cases recur after 5 years. The long-term post-recurrence outcomes remain controversial. To examine the accurate prognostic factors associated with survival and cancer recurrence among 5-year survivors, a landmark analysis that considered competing risks was performed. METHODS: Complete resection of NSCLC was performed in 2482 patients between January 2003 and December 2015. A total of 1431 patients were 5-year survivors without recurrence. A landmark time analysis was applied to the overall survival (OS) and recurrence-free survival (RFS) from 5 years after surgery, and the findings were calculated using the Kaplan-Meier method. The cumulative incidence of cause-specific death and recurrence was estimated using the cumulative incidence function, while carefully considering the competing risks. RESULTS: Postoperative recurrence was detected in 732 patients, of whom 68 (9.3%) had recurrence after 5 years. The median follow-up period was 8.2 years. In the competing risk analysis, the independent poor prognostic factors associated with cause-specific death were age ≥ 75 years, lymph node metastasis and pleural invasion. CONCLUSIONS: Patients requiring a follow-up for > 5 years were aged ≥ 75 years and had either lymph node metastasis or pleural invasion.

Clinicopathological features and prognostic impact of dirty necrosis in metastatic lung cancers from the colon and rectum.

Dirty necrosis (DN) is a form of tumor necrosis (TN) with prominent neutrophil infiltration and cell detritus in the necrotic foci. This study aimed to characterize the clinicopathological features of DN in metastatic lung cancers of the colon and rectum (MLCRs). A total of 227 patients who underwent pulmonary metastasectomy and complete resection for MLCR were included in this study. TN was evaluated using digitally scanned resection specimens. These slides were immunostained for biomarkers of NETosis (citrullinated histone H3 [citH3] and myeloperoxidase [MPO]), and the area positive for citH3 and MPO was further quantified. TN was observed in 216 cases (95.2%), and 54 (25.0%) of these cases had DN. The presence of TN was not associated with a worse prognosis; however, patients with DN had a significantly shorter overall survival than those without DN (p < 0.01). Furthermore, the presence of DN was a poor prognostic factor in both the univariate and multivariate analyses. Immunohistochemical analysis revealed that the percentage of citH3-positive and MPO-positive areas in the DN-positive cases was significantly higher than that in the DN-negative cases (p < 0.01 and p < 0.01, respectively). In surgically resected MLCR, DN is the characteristic TN subtype associated with poor prognosis and neutrophil extracellular traps (NETs).

HLA Class I Analysis Provides Insight Into the Genetic and Epigenetic Background of Immune Evasion in Colorectal Cancer With High Microsatellite Instability.

BACKGROUND & AIMS: A detailed understanding of antitumor immunity is essential for optimal cancer immune therapy. Although defective mutations in the B2M and HLA-ABC genes, which encode molecules essential for antigen presentation, have been reported in several studies, the effects of these defects on tumor immunity have not been quantitatively evaluated. METHODS: Mutations in HLA-ABC genes were analyzed in 114 microsatellite instability-high colorectal cancers using a long-read sequencer. The data were further analyzed in combination with whole-exome sequencing, transcriptome sequencing, DNA methylation array, and immunohistochemistry data. RESULTS: We detected 101 truncating mutations in 57 tumors (50%) and loss of 61 alleles in 21 tumors (18%). Based on the integrated analysis that enabled the immunologic subclassification of microsatellite instability-high colorectal cancers, we identified a subtype of tumors in which lymphocyte infiltration was reduced, partly due to reduced expression of HLA-ABC genes in the absence of apparent genetic alterations. Survival time of patients with such tumors was shorter than in patients with other tumor types. Paradoxically, tumor mutation burden was highest in the subtype, suggesting that the immunogenic effect of accumulating mutations was counterbalanced by mutations that weakened immunoreactivity. Various genetic and epigenetic alterations, including frameshift mutations in RFX5 and promoter methylation of PSMB8 and HLA-A, converged on reduced expression of HLA-ABC genes. CONCLUSIONS: Our detailed immunogenomic analysis provides information that will facilitate the improvement and development of cancer immunotherapy.

Efficacy of Preoperative Biopsy in Predicting the Newly Proposed Histologic Grade of Resected Lung Adenocarcinoma.

A novel histologic grading system for invasive lung adenocarcinomas (LUAD) has been newly proposed and adopted by the World Health Organization (WHO) classification. We aimed to evaluate the concordance of newly established grades between preoperative biopsy and surgically resected LUAD samples. Additionally, factors affecting the concordance rate and its prognostic impact were also analyzed. In this study, surgically resected specimens of 222 patients with invasive LUAD and their preoperative biopsies collected between January 2013 and December 2020 were used. We determined the histologic subtypes of preoperative biopsy and surgically resected specimens and classified them separately according to the novel WHO grading system. The overall concordance rate of the novel WHO grades between preoperative biopsy and surgically resected samples was 81.5%, which was higher than that of the predominant subtype. When stratified by grades, the concordance rate of grades 1 (well-differentiated, 84.2%) and 3 (poorly differentiated, 89.1%) was found to be superior compared to grade 2 (moderately differentiated, 66.2%). Overall, the concordance rate was not significantly different from biopsy characteristics, including the number of biopsy samples, biopsy sample size, and tumor area size. On the other hand, the concordance rate of grades 1 and 2 was significantly higher in tumors with smaller invasive diameters, and that of grade 3 was significantly higher in tumors with larger invasive diameters. Preoperative biopsy specimens can predict the novel WHO grades, especially grades 1 and 3 of surgically resected specimens, more accurately than the former grading system, regardless of preoperative biopsy or clinicopathologic characteristics.

The prognostic impact of a high number of peritumoral alveolar macrophages in neuroendocrine carcinoma in the lung.

Alveolar macrophages (AMs) are resident macrophages in the lungs; however, whether the number of AMs plays a role in the lung neuroendocrine tumor (NET) prognosis remains unclear. We counted the number of AMs located around the tumor (peritumoral alveolar macrophages [pAMs]) and the number of AMs located apart from the tumor (distant macrophages; dAMs). In 73 cases of neuroendocrine carcinoma (NEC: small cell lung carcinoma and large cell neuroendocrine carcinoma), the group that contained higher pAMs (≥86/µm2 ) revealed shorter recurrent-free survival (RFS) than those with lower pAMs (<86/µm2 ) (p = 0.005). Bivariate analysis showed that the number of pAMs was an independent predictor of a poor RFS. In contrast, in the carcinoid tumor cohort (n = 29), there was no statistically significant correlation between the two groups with high and low numbers of pAMs in RFS (p = 0.113). Furthermore, we examined the correlation between genomic alterations and the number of pAMs in NEC, but no significant correlation was observed. In conclusion, the number of pAMs is a prognostic factor for NEC in the lung and pAMs may contribute to tumor progression within the peritumoral microenvironment.

Tumor size exceeding 5 cm as a valid prognostic factor in all stages of thymic epithelial tumors.

PURPOSE: This study investigated the prognostic factors of thymic epithelial tumors (TETs) to identify patients who require multidisciplinary treatment and improve the TET prognosis. METHODS: We retrospectively reviewed the data of 268 TET patients. Prognostic variables for the overall survival (OS) were analyzed in all TET stages (n = 268), and the recurrence-free survival (RFS) was analyzed in patients who achieved complete resection (n = 164). RESULTS: The median follow-up period was 7 years; thymic carcinomas (TCs) and advanced stages of tumor, node, and metastasis (TNM) classification had the worse prognosis according to a Kaplan-Meier analysis. The cut-off value of the tumor size to predict the OS and RFS was determined using modified Harrell's c-index calculated by a Cox regression analysis of the OS. Regarding the OS, a multivariate analysis revealed that age > 70 years old (p = 0.011), tumor size > 5 cm (p < 0.001), and TCs (p = 0.002) were significant prognostic factors aside from the TNM stage (p < 0.001). Regarding the RFS, tumor size > 5 cm was the only significant prognostic factor in the multivariate analysis (p = 0.002) aside from the TNM stage (p = 0.008). CONCLUSIONS: Tumor size > 5 cm was shown to be a prognostic predictor in addition to the WHO and TNM classifications. Therefore, multidisciplinary treatment should be developed for TET patients with poor prognostic factors, specifically tumor size.

18F-fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma.

Positron emission tomography is a useful technique for diagnosing lymph node (LN) metastasis. This study aimed to elucidate the association between fluorodeoxyglucose accumulation and the microenvironment in metastatic LNs in lung adenocarcinoma. We retrospectively analyzed 62 patients with surgically resected pathological N2 lung adenocarcinoma who underwent preoperative PET. The maximum standardized uptake value (SUVmax ) in the metastatic LNs was measured. Lymph node specimens were immunohistochemically analyzed for CD8+ , FoxP3+ , and CD79a+ lymphocytes, CD204+ tumor-associated macrophages (TAMs), and alpha-smooth muscle actin-positive cancer-associated fibroblasts (αSMA+ CAFs). We compared the clinicopathologic and immunohistochemical characteristics between two groups with high and low LN SUVmax . Using novel 3D hybrid spheroid models, we investigated the change in invasiveness of cancer cells in the presence of CAFs. In the multivariate analyses, LN SUVmax was an independent prognostic factor. The overall survival in the LN SUVmax high group was significantly worse than in the low group (P = .034). In the LN SUVmax high group, metastatic cancer cell invasion of extranodal tissue was more frequent (P = .005) and the number of CD204+ TAMs and αSMA+ CAFs in metastatic LNs was significantly higher than in the low group (P < .001 and P = .002, respectively). Hybrid spheroid models revealed that cancer cells coexisting with CAFs were more invasive than those without CAFs. Our results indicated a strong association between LN SUVmax and poor prognosis in patients with N2 lung adenocarcinoma. Moreover, LN SUVmax was suggested to be associated with the presence of tumor-promoting stromal cells in metastatic LNs.

Prognostic impact of count of extratumoral lymphatic permeation in lung adenocarcinoma and its relation to the immune microenvironment.

Extratumoral lymphatic permeation (ly-ext) has been reported as an independent poor prognostic factor for lung adenocarcinoma, but whether or not the number of ly-ext foci is associated with prognosis and its relationship to the immune microenvironment is unclear. We counted the number of ly-ext foci on pathological slides from patients with completely resected lung adenocarcinoma with ly-ext, and divided them into two groups: a group with a high number of ly-ext foci (ly-ext high) and one with a low number of ly-ext foci (ly-ext low). Among the patients with ly-ext, only a high number of ly-ext foci was an independent poor prognostic factor. The 3-year recurrence-free survival (RFS) rate of the ly-ext high group was significantly lower than that of the ly-ext low group (14.7% vs. 50.0%, P < 0.01). Then, we analyzed the immune microenvironment of pT1 lung adenocarcinoma with ly-ext (13 cases of ly-ext high and 11 cases of ly-ext low tumor) by immunohistochemistry using antibodies for stem cell markers (aldehyde dehydrogenase 1 A1 and CD44), tumor-promoting mucin (MUC1), tumor-infiltrating lymphocytes (CD4, CD8, FOXP3, and CD79a), and tumor-associated macrophages (CD204). The number of CD8+ TILs within the primary lesion was significantly lower and the number of FOXP3+ TILs within the primary lesion was significantly higher in the ly-ext high group (P < 0.05 and P < 0.01, respectively). Our results indicated that a high number of ly-ext foci was an independent poor prognostic factor. Moreover, tumors with high numbers of ly-ext foci had a more immunosuppressive microenvironment.

Correlation between the number of viable tumor cells and immune cells in the tumor microenvironment in non-small cell lung cancer after induction therapy.

This study aims to determine the correlation between the percent viable tumor cells (%VTC) and the tumor microenvironment in resected non-small cell lung cancer after induction therapy. We enrolled 72 patients with non-small cell lung cancer (NSCLC) who received chemoradiotherapy (CRT) or chemotherapy (CT) prior to surgery. The ratio of the area of viable tumor cells to the total tumor area was calculated to obtain the %VTC. We also examined the number of CD4 (+), CD8 (+), CD20 (+) and FOXP3 (+) tumor-infiltrating lymphocytes (TILs), podoplanin (PDPN) (+) cancer-associated fibroblasts (CAFs), and CD204 (+) tumor-associated macrophages (TAMs) by immunohistochemistry (IHC). In the CRT group (n = 37), the tumors had significantly lower %VTC than the CT group (n = 35) (P < 0.001). In both of the CT group and CRT group, the %VTC showed a significant positive correlation with the number of CD204 (+)-TAMs (P = 0.014 and 0.005, respectively). Only in the CRT group, a higher number of CD204 (+) TAMs was associated with a shorter overall survival (OS) (P = 0.007) and recurrence-free survival (RFS) (P = 0.015). In the CRT group, the number of CD204 (+) TAMs is associated with %VTC and prognosis, suggesting that these cells may have tumor-promoting effects on the residual lung cancer in specific microenvironments after CRT.

Continuation of aspirin perioperatively for lung resection: a propensity matched analysis.

PURPOSE: To clarify the safety and effectiveness of continuing aspirin during the perioperative period of lung resection. METHODS: We analyzed, retrospectively, consecutive patients who underwent lung resection between 2008 and 2017. To investigate the safety of aspirin continuation, patients who continued taking aspirin perioperatively (Group C) were matched to other patients (Group O), using a propensity score, and bleeding outcomes were compared. To assess the effect of aspirin interruption, Group C was matched to a group of patients whose aspirin regimen was interrupted (Group I), and the postoperative complications related to thromboembolism were compared. RESULTS: Among 3393 patients, 52 continued on aspirin (Group C) perioperatively, whereas 184 had their aspirin discontinued (Group I). Comparing the matched cohorts extracted from Group C and Group O (n = 45), there were no significant differences in bleeding outcomes. Comparing the matched cohorts extracted from Group C and Group I (n = 40), group C had fewer postoperative complications related to thromboembolism (0% vs. 7.5%, p = 0.039). CONCLUSION: Bleeding complications did not increase by continuing aspirin, but thromboembolic complications increased when the aspirin regimen was interrupted during the perioperative period of lung resection. Thus, in the absence of a prohibitive bleeding risk, the continuation of aspirin during the perioperative period of lung resection appears to be desirable.

Prognostic impact of home oxygen therapy on patients with resected non-small-cell lung cancer with interstitial lung disease.

PURPOSE: Non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) have a poor prognosis. The present study evaluated the prognostic impact of home oxygen therapy (HOT) in NSCLC patients with ILD. METHODS: Overall, 3099 consecutive patients underwent complete resection of stage IA to IIIA NSCLC at our institution between 2002 and 2016. ILD was diagnosed and categorized based on high-resolution computed tomography. The criteria for HOT included less than 90% resting oxygen saturation in the peripheral arteries and severe exertional dyspnea. We retrospectively compared the overall survival between ILD patients with and without HOT. RESULTS: ILD was observed in 150 (5%) patients. Seventeen (11%) patients needed HOT at discharge. The incidences of usual interstitial pneumonia (UIP) pattern (p = 0.03) and blood loss (p < 0.01) were significantly higher in the patients requiring HOT than in those without HOT. Significantly more patients developed complications (p = 0.04) in the HOT group than in the non-HOT group, with three (18%) having acute exacerbations. The 3-year overall survival rate was significantly lower in the HOT patients than in those without HOT (28% vs. 63%, p = 0.03). CONCLUSIONS: Patients requiring postoperative HOT showed a significantly poorer prognosis after complete resection than those without HOT. Therefore, the indication for surgery should be investigated cautiously in order to prevent the need for postoperative HOT.

Pathological features and prognostic implications of ground-glass opacity components on computed tomography for clinical stage I lung adenocarcinoma.

PURPOSE: To investigate the prognostic implications and pathological features of clinical stage I lung adenocarcinoma with ground-glass opacity (GGO) on computed tomography (CT). METHODS: The subjects of this retrospective study were 1228 patients with lung adenocarcinoma classified as clinical stage I, who underwent complete resection by lobectomy. The patients were divided into four groups based on the presence and proportion of GGO according to the consolidation-to-tumor ratio (CTR); A, CTR ≤ 0.5; B, 0.5 < CTR ≤ 0.75; C, 0.75 < CTR ≤ 1.0 with GGO; D, without GGO (pure-solid). We compared overall survival, pathological findings (N/ly/v/STAS), and histological subtypes within each clinical stage among the four groups. RESULTS: We found no significant differences among tumors with GGO (groups A, B and C) for prognosis or pathological findings in all the clinical stages. The prognoses of groups A, B and C were significantly better than that of group D for patients with clinical stages IA2-IB disease. Tumors without GGO on CT had a significantly larger number of positive N, ly, v and STAS in almost all stages than tumors with GGO on CT. Tumors without GGO on CT had significantly more solid predominant and less lepidic predominant adenocarcinoma. CONCLUSION: Not the proportion of GGO, but its presence on CT, as well as the size of the solid component, were correlated significantly with pathological characteristics and survival.

Perioperative pirfenidone treatment as prophylaxis against acute exacerbation of idiopathic pulmonary fibrosis: a single-center analysis.

PURPOSE: Lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis and postoperative acute exacerbation (AE) of IPF is a fatal complication. Studies have shown that perioperative pirfenidone treatment (PPT) may reduce the incidence of AE-IPF. We evaluated the efficacy of PPT in preventing AE-IPF and improving overall survival. METHODS: The subjects of this study were 56 patients with IPF who underwent resection of lung cancer in our hospital between January, 2011 and September, 2016. Pirfenidone was administered to patients from 4 weeks before the operation and continued for longer periods. Thirty-six patients received PPT and their outcome was compared with that of the other 20 patients who did not. RESULTS: There were no differences in age, gender, smoking history, respiratory function, or surgical procedures between the groups. AE-IPF developed in three patients (8%) in the PPT group and four (20%) patients in the non-PPT group, without a significant difference between the groups. The interval was significantly longer in the PPT group (p = 0.03). PPT reduced postoperative mortality significantly (p = 0.04). CONCLUSIONS: Although perioperative pirfenidone treatment did not obviously prevent postoperative AE-IPF, it may reduce the mortality of lung cancer patients with IPF.

Proportion of goblet cell is associated with malignant potential in invasive mucinous adenocarcinoma of the lung.

Invasive mucinous adenocarcinoma (IMA) is a newly classified variant of lung adenocarcinoma. The aim of this study was to examine the correlation between the proportion of goblet cells and the clinicopathological characteristics of IMA. Ninety-nine patients with stage I IMA were included in this study. We estimated prognostic impact of goblet cell proportion. We classified them into two groups: the cases with a high goblet cell proportion (HGP, goblet cell proportion ≥80%) and the cases with a low goblet cell proportion (LGP, goblet cell proportion ≤30%), and compared the expression levels of five cancer progression markers and the number of tumor-promoting stromal cells between the two groups. Univariate and multivariate analysis revealed that the goblet cell proportion was a prognostic factor for recurrence free survival (P < 0.01) and overall survival (P = 0.01). The expression levels of the cancer stem cell-related marker, ALDH-1, and proliferation-related marker, geminin were significantly higher in the LGP group than in the HGP group. CD204+ tumor-associated macrophages were significantly more in the LGP stroma than the HGP stroma. Our current study indicated that the proportion of goblet cells was correlated with the malignant potential in surgically resected IMA.