analysis was performed using a Cox proportional hazard ratio (HR) model to estimate the adjusted HR for each prognostic factor.RESULTS: A total of 2,988 MBC patients were enrolled and followed-up for a median of 100 months (range, 2–324 months). Multivariate analysis revealed that axillary lymph node (ALN) metastasis and estrogen receptor (ER) negativity were significant prognostic factors for BCSS. Meanwhile, old age, pathologic tumor stage, and ALN metastasis were significant prognostic factors for OS. Subgroup analysis of ER-positive MBC showed that ALN metastasis was a significant prognostic factor for BCSS. Additionally, old age, pathologic tumor stage, and ALN metastasis were prognostic factors for OS. Ultimately, ALN metastasis was the most statistically significant prognostic factor for MBC. However, chemotherapy had no significant effect on BCSS and OS. The Kaplan-Meier curves of BCSS and OS based on pathologic tumor and nodal stages and age revealed that chemotherapy did not statistically significantly improve prognosis, except for the N3 stage.CONCLUSION: Our large retrospective analysis revealed that adjuvant chemotherapy provided little benefit to improve the prognosis of most ER-positive MBC patients. Therefore, chemotherapy can be omitted in the treatment of most ER-positive MBC.]]>
Adenocarcinoma, Mucinous ; Breast Neoplasms ; Breast ; Carcinoma, Ductal ; Chemotherapy, Adjuvant ; Diagnosis ; Drug Therapy ; Estrogens ; Humans ; Lymph Nodes ; Methods ; Mucins ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies

OBJECTIVE: To determine the accuracy of frozen section diagnosis and factors associated with final pathological diagnosis upgrade in patients with mucinous ovarian tumors. METHODS: This study included 1,032 patients with mucinous ovarian tumors who underwent frozen section diagnosis during surgery. Sensitivity, specificity, and diagnostic accuracy of frozen section diagnosis was calculated. Univariate and multivariate regression analyses were performed to determine factors associated with diagnosis upgrade in the final pathology report. RESULTS: The sensitivity and specificity of frozen section diagnosis were 99.1% (95% confidence interval [CI]=98%–99.6%) and 82.2% (95% CI=77.9%–85.7%), respectively, for benign mucinous tumors; 74.6% (95% CI=69.1%–79.4%) and 96.7% (95% CI=95.2%–97.8%), respectively, for mucinous borderline ovarian tumors; and 72.5% (95% CI=62.9%–80.3%) and 98.8% (95% CI=97.9%–99.3%), respectively, for invasive mucinous carcinomas. The multivariate analysis revealed that mixed tumor histology (odds ratio [OR]=2.8; 95% CI=1.3–6.3; p=0.012), tumor size >12 cm (OR=2.5; 95% CI=1.5–4.3; p=0.001), multilocular tumor (OR=2.9; 95% CI=1.4–6.0; p=0.006), and presence of a solid component in the tumor (OR=3.1; 95% CI=1.8–5.1; p<0.001) were independent risk factors for final pathological diagnosis upgrade. CONCLUSIONS: Mixed tumor histology, tumor size >12 cm, multilocular tumor, and presence of a solid component in the tumor were independent risk factors for final pathological diagnosis upgrade based on frozen section diagnosis.
Adenocarcinoma, Mucinous ; Diagnosis ; Frozen Sections ; Humans ; Mucins ; Multivariate Analysis ; Ovarian Neoplasms ; Pathology ; Risk Factors ; Sensitivity and Specificity

OBJECTIVE: To evaluate the efficacy of the morphologic-metabolic (M-M) dissociation sign based on computed tomography (CT) and fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/CT in discriminating invasive mucinous adenocarcinoma (IMA) from invasive non-mucinous adenocarcinomas (ADCs) of the lung. MATERIALS AND METHODS: The Institutional Review Board approved this retrospective study. Among surgically resected solitary pulmonary nodule (SPN)-type ADCs (< 3 cm in diameter), 35 patients with IMAs and 329 with invasive non-mucinous ADCs were included. Morphologic malignancy was established if the tumor with lobulated or spiculated margin on CT presented a tumor shadow disappearance rate of < 0.5. The M-M dissociation sign was determined when a malignant-morphologic nodule on CT showed maximum standardized uptake value (SUVmax) < 3.5 on PET/CT. RESULTS: Among 35 IMAs (size: 21 ± 7 mm, SUVmax: 1.8 ± 2.0) and 329 invasive non-mucinous ADCs (size: 21 ± 6 mm, SUVmax: 4.6 ± 4.2), the M-M dissociation sign was observed in 54% of IMAs (19/35) and 10% of invasive non-mucinous ADCs (34/329) (p < 0.001). The diagnostic performance of the sign in discriminating IMA from invasive non-mucinous ADCs showed a sensitivity of 54.3% (95% confidence interval [CI], 36.7–71.2), specificity 89.7% (95% CI, 85.9–92.7), positive predictive value 35.8% (95% CI, 26.5–46.5), and negative predictive value 94.9% (95% CI, 92.8–96.4). Multivariate analyses revealed metabolic benignity (odds ratio [OR] 2.99; 95% CI, 1.01–8.93; p = 0.047) and M-M dissociation sign (OR 6.35; 95% CI, 2.76–14.62; p < 0.001) to be significant predictors of SPN-type IMAs. CONCLUSION: Identification of the absence of M-M dissociation sign is an accurate indicator for excluding IMA from SPN-type lung ADCs.
Adenocarcinoma ; Adenocarcinoma, Mucinous ; Diagnosis ; Ethics Committees, Research ; Fluorodeoxyglucose F18 ; Humans ; Lung ; Mucins ; Multivariate Analysis ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Retrospective Studies ; Sensitivity and Specificity ; Solitary Pulmonary Nodule

PURPOSE: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological para-meters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. METHODS: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. RESULTS: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases ( < 5%), 31 cases (6%–25%), 48 cases (26%–50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p < 0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p < 0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p < 0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296–0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314–0.3912; p=0.0006). CONCLUSION: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.
Antibodies ; Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Disease-Free Survival ; Humans ; Immunoglobulins* ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating* ; Mucin-3* ; Mucins* ; Multivariate Analysis ; Prognosis ; Recurrence ; T-Lymphocytes* ; Triple Negative Breast Neoplasms*

BACKGROUND/AIMS: Presence of enhanced mural nodules, which can be visualized using computed tomography (CT), is one of high-risk stigmata in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs). Conversely, the absence of enhanced mural nodules on preoperative imaging does not exclude malignant risk. The present study aimed to investigate other morphological features as predictors of malignancy in “pure” BD-IPMNs without enhanced mural nodules on CT. METHODS: This retrospective study included 180 patients with surgically confirmed “pure” BD-IPMNs of the pancreas and no enhanced mural nodules on preoperative CT. The study was conducted at 15 tertiary referral centers throughout South Korea. Univariate and multivariate analyses were used to identify significant predictors of malignancy. RESULTS: BD-IPMNs with low-grade (n=84) or moderate-grade (n=76) dysplasia were classified as benign; those with high-grade dysplasia (n=8) or invasive carcinoma (n=12) were classified as malignant. The multivariate analysis revealed that cyst size ≥30 mm (odds ratio, 8.6; p=0.001) and main pancreatic duct diameter ≥5 mm (odds ratio, 4.1; p=0.01) were independent risk factors for malignancy in “pure” BD-IPMNs without enhanced mural nodules on CT. Endoscopic ultrasound detected enhanced mural nodules (6/82) that had been missed on CT, and two IPMNs with enhanced mural nodules were malignant. CONCLUSIONS: In patients with “pure” BD-IPMNs who have no enhanced mural nodules on CT, cyst size ≥30 mm and main pancreatic duct diameter ≥5 mm may be associated with malignancy.
Christianity ; Humans ; Korea ; Mucins* ; Multivariate Analysis ; Pancreas* ; Pancreatic Ducts ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers ; Ultrasonography

PURPOSE: Mucinous adenocarcinomas account for about 10% of all colorectal cancers. This study aimed to investigate the prognostic impact of mucinous histologic subtype on oncologic outcomes in patients with colorectal cancer. METHODS: This retrospective study was performed at two large tertiary university hospitals. We analyzed the characteristics, prognostic factors, and survival of patients with colorectal cancer who were treated and followed up between 2000 and 2013. RESULTS: Totally, 144 of 1,268 patients with a colorectal adenocarcinoma (11.4%) had mucinous histologic subtype. Statistically significant results found in this research are as follows: Mucinous histologic subtype tended to present in younger patients and to have larger tumor size, higher histologic grade, higher node stage, larger number of positive nodes, and higher rate of perineural invasion compared to nonmucinous histologic subtype. On the univariate analysis, mucinous subtype was a prognostic factor for disease-free and overall survival. On the multivariate analysis, primary tumor location, node stage and lymphatic-vascular invasion were independent prognostic factors for the local control rate. Rectal tumor location, higher disease stage, tumor grade II, and presence of lymphatic-vascular invasion had negative influences on disease-free survival, as did rectal tumor location, higher disease stage and presence of lymphatic-vascular invasion on overall survival. CONCLUSION: Mucinous histologic subtype was associated with some adverse pathologic features in patients with colorectal cancer; however, it was not an independent prognostic factor for oncologic outcome.
Adenocarcinoma ; Adenocarcinoma, Mucinous ; Colorectal Neoplasms* ; Disease-Free Survival ; Hospitals, University ; Humans ; Mucins* ; Multivariate Analysis ; Prognosis ; Rectal Neoplasms ; Retrospective Studies ; Survival Rate ; Treatment Outcome

BACKGROUND: We reviewed a series of 188 resected pulmonary mucinous adenocarcinomas (MAs) to clarify the prognostic significance of lepidic and non-lepidic patterns. METHODS: Non-lepidic patterns were divided into bland, non-distorted acini with uncertain invasiveness (pattern 1), unequivocal invasion into stroma (pattern 2), or invasion into alveolar spaces (pattern 3). RESULTS: The mean proportion of invasive patterns (patterns 2 and 3) was lowest in small (≤ 3 cm) tumors, and gradually increased in intermediate (> 3 cm and ≤ 7 cm) and large (> 7 cm) tumors (8.4%, 34.3%, and 50.1%, respectively). Adjusted T (aT) stage, as determined by the size of invasive patterns, was positively correlated with adverse histologic and clinical features including older age, male sex, and ever smokers. aTis tumors, which were exclusively composed of lepidic pattern (n = 9), or a mixture of lepidic and pattern 1 (n = 40) without any invasive patterns, showed 100% disease- free survival (DFS). The aT1mi tumors, with minimal (≤ 5 mm) invasive patterns (n = 63), showed a 95.2% 5-year DFS, with recurrences (n = 2) limited to tumors greater than 3 cm in total size (n = 23). Both T and aT stage were significantly associated with DFS; however, survival within the separate T-stage subgroups was stratified according to the aT stage, most notably in the intermediatestage subgroups. In multivariate analysis, the size of invasive patterns (p = .020), pleural invasion (p < .001), and vascular invasion (p = .048) were independent predictors of recurrence, whereas total size failed to achieve statistical significance (p = .121). CONCLUSIONS: This study provides a rationale for histologic risk stratification in pulmonary MA based on the extent of invasive growth patterns with refined criteria for invasion.
Adenocarcinoma in Situ ; Adenocarcinoma, Mucinous* ; Disease-Free Survival ; Humans ; Lung ; Male ; Mucins* ; Multivariate Analysis ; Recurrence*

OBJECTIVETo investigate the effect of annexin A2 (AnxA2) on epithelial growth factor receptor (EGFR)/nuclear factor-κB (NF-κB) signal transduction and mucin expression in human airway epithelial H292 cells treated with Mycoplasma pneumoniae (MP).

METHODSH292 cells were divided into control group, MP group, NC-siRNA+MP group, and AnxA2 siRNA+MP group. The cells in the MP group were incubated with 5 μg/mL MP antigen for 2 hours. The cells in the NC-siRNA+MP and AnxA2 siRNA+MP groups were transfected with NC-siRNA and AnxA2 siRNA for 24 hours, followed by MP antigen stimulation for 2 hours. The MTT method was used to measure cell viability; quantitative real-time PCR was used to measure the mRNA expression of AnxA2; Western blot was used to measure the protein expression of AnxA2, phosphorylated EGFR (p-EGFR), and phosphorylated p65 NF-κB (p-p65 NF-κB); ELISA was used to measure the secretion of mucin 5AC (MUC5AC) and mucin 5B (MUC5B).

RESULTSThe MP and NC-siRNA+MP groups had lower cell viability than the control group (P<0.05). The AnxA2 siRNA+MP group had higher cell viability than the MP and NC-siRNA+MP groups and lower cell viability than the control group (P<0.05). The MP and NC-siRNA+MP groups had significantly higher mRNA and protein expression of AnxA2 than the AnxA2 siRNA+MP group (P<0.05). Compared with the control group, the MP and NC-siRNA+MP groups had significant increases in the protein expression of p-EGFR, p-p65 NF-κB, MUC5AC, and MUC5B (P<0.05); the AnxA2 siRNA+MP group had lower protein expression than the MP and NC-siRNA+MP groups, but higher protein expression than the control group (P<0.05).

CONCLUSIONSAnxA2 is involved in the airway lesion induced by MP antigen via mediating EGFR/NF-κB signaling activation and mucin expression in human airway epithelial cells.

Annexin A2 ; physiology ; Bronchi ; physiology ; Cells, Cultured ; Epithelial Cells ; microbiology ; Humans ; Mucins ; analysis ; Mycoplasma pneumoniae ; pathogenicity ; NF-kappa B ; physiology ; Receptor, Epidermal Growth Factor ; physiology ; Signal Transduction ; physiology

BACKGROUND: Mucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. METHODS: A total of 64 patients with invasive breast cancer with mucinous or micropapillary features were enrolled in the study. Of 36 pure mucinous carcinomas, 17 (47.2%) had micropapillary features and were termed mucinous carcinoma with micropapillary features (MUMPC), and 19 (52.8%) had no micropapillary features and were termed mucinous carcinoma without micropapillary features. MUMPC were compared with 15 invasive micropapillary carcinomas (IMPC) and 13 invasive ductal and micropapillary carcinomas (IDMPC). RESULTS: The clinicopathological factors of pure mucinous carcinoma and MUMPC were not significantly different. In contrast to IMPC and IDMPC, MUMPC had a low nuclear grade, lower mitotic rate, higher expression of hormone receptors, negative human epidermal growth factor receptor 2 (HER2) status, lower Ki-67 proliferating index, and less frequent lymph node metastasis (p < .05). According to univariate analyses, progesterone receptor, HER2, T-stage, and lymph node metastasis were significant risk factors for overall survival; however, only T-stage remained significant in a multivariate analysis (p < .05). CONCLUSIONS: In contrast to IMPC and IDMPC, the micropapillary pattern in mucinous carcinoma does not contribute to aggressive behavior. However, further analysis of a larger series of patients is required to clarify the prognostic significance of micropapillary patterns in mucinous carcinoma of the breast.
Adenocarcinoma, Mucinous* ; Breast Neoplasms ; Breast* ; Humans ; Lymph Nodes ; Mucins* ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Risk Factors

PURPOSE: Mucinous cells (MUCs), signet-ring cells (SRCs), and poorly differentiated cells (PDCs) are uncommon histologic types and have been associated with advanced tumor stage and poor prognosis. However, MUCs, SRCs, and PDCs are commonly observed in cancers with high microsatellite instability (MSI), which have favorable outcomes compared with cancers with microsatellite stability (MSS). The purpose of this study was to evaluate the prognostic impact of high-MSI in patients with sporadic colorectal cancer presenting with MUCs, SRCs, and/or PDCs. METHODS: Between January 2006 and December 2012, 176 with proven microsatellite status who also presented with MUCs, SRCs, and PDCs were selected for this study and were divided into 2 groups, high-MSI and MSS; their outcomes were analyzed. RESULTS: Of the 176 patients, 56 and 120, respectively, had high-MSI and MSS cancers. High-MSI cancers had larger tumors, proximal tumor location, and a lower TNM stage. The recurrence rate was lower in the high-MSI group (13.7% vs. 35.4%, P = 0.006). Common patterns of distant metastasis for MUC, SRC, PDC cancers were peritoneal spread (46.9%) and hematogenous metastasis (46.4%). The 5-year CSS rates were 88.2% and 61.2% for patients with high-MSI and MSS cancers, respectively (P < 0.0001). In the multivariate analysis, except for stage-IV cancer, MSI status was an independent risk factor for cancer-specific survival (MSS: hazard ratio, 4.34; 95% confidence interval, 1.68-11.21). CONCLUSION: In patients with colorectal cancer presenting with MUCs, SRCs, and/or PDCs, those with high-MSI cancers had better outcomes.
Colorectal Neoplasms* ; Humans ; Microsatellite Instability* ; Microsatellite Repeats* ; Mucins* ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Risk Factors