MRI features and texture analysis for the early prediction of therapeutic response to neoadjuvant chemoradiotherapy and tumor recurrence of locally advanced rectal cancer.

OBJECTIVES: This study aimed to evaluate the efficiency of imaging features and texture analysis (TA) based on baseline rectal MRI for the early prediction of therapeutic response to neoadjuvant chemoradiotherapy (nCRT) and tumor recurrence in patients with locally advanced rectal cancer (LARC). METHODS: Consecutive patients with LARC who underwent rectal MRI between January 2014 and December 2015 and surgical resection after completing nCRT were retrospectively enrolled. Imaging features were analyzed, and TA parameters were extracted from the tumor volume of interest (VOI) from baseline rectal MRI. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the optimal TA parameter cutoff values to stratify the patients. Logistic and Cox regression analyses were performed to assess the efficacy of each imaging feature and texture parameter in predicting tumor response and disease-free survival. RESULTS: In total, 78 consecutive patients were enrolled. In the logistic regression, good treatment response was associated with lower tumor location (OR = 13.284, p = 0.012), low Conv_Min (OR = 0.300, p = 0.013) and high Conv_Std (OR = 3.174, p = 0.016), Shape_Sphericity (OR = 3.170, p = 0.015), and Shape_Compacity (OR = 2.779, p = 0.032). In the Cox regression, a greater risk of tumor recurrence was related to higher cT stage (HR = 5.374, p = 0.044), pelvic side wall lymph node positivity (HR = 2.721, p = 0.013), and gray-level run length matrix_long-run low gray-level emphasis (HR = 2.268, p = 0.046). CONCLUSIONS: Imaging features and TA based on baseline rectal MRI could be valuable for predicting the treatment response to nCRT for rectal cancer and tumor recurrence. KEY POINTS: • Imaging features and texture parameters of T2-weighted MR images of rectal cancer can help to predict treatment response and the risk for tumor recurrence. • Tumor location as well as conventional and shape indices of texture features can help to predict treatment response for rectal cancer. • Clinical T stage, positive pelvic side wall lymph nodes, and the high-order texture parameter, GLRLM_LRLGE, can help to predict tumor recurrence for rectal cancer.

Role of autophagy-related protein expression in patients with rectal cancer treated with neoadjuvant chemoradiotherapy.

BACKGROUND: Autophagy, a cellular degradation process, has complex roles in tumourigenesis and resistance to cancer treatment in humans. The aim of this study was to explore the expression levels of autophagy-related proteins in patients with rectal cancer and evaluate their clinical role in the neoadjuvant chemoradiotherapy setting. METHODS: All specimens evaluated were obtained from 101 patients with colorectal cancer who had undergone neoadjuvant chemoradiotherapy and curative surgery. The primary outcomes measured were the expression levels of two autophagy-related proteins (microtubule-associated protein 1 light chain 3 beta (LC3ß) and beclin-1) by immunohistochemistry and their association with clinicopathological parameters and patient survival. RESULTS: Among the 101 patients, the frequency of high expression of beclin-1 was 31.7% (32/101) and that of LC3ß was 46.5% (47/101). A pathologic complete response was inversely associated with LC3ß expression (P = 0.003) and alterations in the expression of autophagy-related proteins (P = 0.046). In the multivariate analysis, however, autophagy-related protein expression did not show prognostic significance for relapse-free survival or overall survival. CONCLUSIONS: High expression of autophagy-related proteins shows a strong negative association with the efficacy of neoadjuvant chemoradiotherapy in patients with rectal cancer. Autophagy has clear implications as a therapeutic target with which to improve the efficacy of neoadjuvant chemoradiotherapy.

Expression of histone deacetylases in diffuse large B-cell lymphoma and its clinical significance.

BACKGROUND: Histone deacetylase inhibitors are a new class of drugs used in treatment of malignant tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma, and it accounts for more than 40% of all B-cell lymphomas. In this study, we aimed to determine the expression patterns of histone deacetylases (HDACs) in DLBCL, to examine whether HDAC expression patterns differ among cases, and to assess whether these findings have clinical significance. MATERIALS AND METHODS: We selected 91 cases of DLBCL diagnosed at St. Vincent Hospital, The Catholic University of Korea, from 2001-2012. We performed a pathology slide review and collected clinical data including age, sex, tumor site, survival time, and mortality. Immunohistochemical analysis was performed using primary antibodies for HDACs, including HDAC1 and 2 of class I, HDAC4 and 5 of class IIa, and HDAC6 of class IIb. Expression site was determined to be nuclear, cytoplasmic, or both. Staining intensities were graded as low and high. We assessed correlations between HDAC expression levels and clinical data and survival analysis. RESULTS: Of the 91 cases examined, 46 (50.5%) were men and 45 (49.5%) were women. Most of the patients were elderly, and 74 (81.3%) cases were older than 46 y. Forty-six (50.5%) cases showed lymph node involvement, and 45 (49.5%) cases showed lymphoma at extranodal sites. In nodal lymphoma, staining was strongly positive for HDAC2, whereas staining was weak or negative for HDAC4; however, there was no significant correlation with survival. But nodal lymphoma cases with high nuclear expression of HDAC2 and nodal lymphoma cases with high nuclear expression of HDAC2 and low nuclear expression of HDAC4 showed significantly shorter survival times compared with other cases. CONCLUSIONS: High nuclear expression of HDAC2 may play an important role in survival of DLBCL patients, especially in those with nodal lymphoma, which is associated with a shorter survival time. Our results may have important implications for treatment of DLBCL by epigenetic regulation.

Calcifying fibrous tumor presenting as rectal submucosal tumor: first case reported in rectum.

Calcifying fibrous tumor (CFT) is a recently recognized rare benign lesion characterized by dense hyalinized collagenous tissue with interspersed spindle cells and a lymphoplasmocytic infiltrate. Calcification is the hallmark of CFT and may present in the form of psammomatous bodies or dystrophic calcifications. CFT of the intestinal tract is uncommon and rectal CFT has never been reported. Recently, we experienced a case of CFT found in the rectum of a 36-year-old man. In this study, we described the characteristic histopathological findings with a review of the relevant literature. Although CFT of the intestinal tract as an intrinsic visceral lesion is unusual and clinically unexpected, CFT should be considered in the differential diagnosis of rectal submucosal tumor.

Accuracy of preoperative T2 gallbladder tumor localization and the adequate surgical resection.

INTRODUCTION: The agreement between the radiologic and histopathologic tumor locations in T2 gallbladder cancer is critical. There is no consensus regarding the extent of curative resection by tumor locations. METHODS: Between January 2010 and December 2019, a consecutive series of 118 patients with pathological T2 gallbladder cancer who underwent surgery were retrospectively analyzed in terms of the accordance between radiologic and histopathologic tumor locations, the extents of hepatic resection and the numbers of harvested lymph nodes. Radical resection was defined as liver resection with harvesting of at least four lymph nodes. RESULTS: The accuracy of preoperative tumor localization was only 68%. After radical resection, the 5-year overall survival (OS) was 59.4%; after nonradical resection, the figure was 46.1% (p = 0.092). In subanalyses, the 5-year OS was marginally better for patients who underwent liver resection or from whom at least four lymph nodes were harvested than those who did not undergo liver resection or from whom three or fewer lymph nodes were harvested (58.2% vs. 39.4%, p = 0.072; 59.9% vs. 50.0%, p = 0.072, respectively). In patients with peritoneal side tumor, the 5-year OSs of those who did and did not undergo liver resection were 67% and 41.2%, respectively (p = 0.028). In multivariate analysis, perineural invasion and radical resection were independently prognostic of OS. CONCLUSION: The accuracy of preoperative tumor localization was 68%. Hepatic resection, lymph node dissection harvesting of at least four lymph nodes are required for curative resection for gallbladder cancer, regardless of tumor location.

Glucose transporter 1 (GLUT1) of anaerobic glycolysis as predictive and prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for locally advanced rectal cancer.

PURPOSE: We investigated the relationships between biomarkers related to anaerobic glycolytic metabolism (GLUT1, LDH5, PDK1, and HIF-1α proteins), pathologic response, and prognosis. METHODS: All stage II and stage III rectal cancer patients had 50.4 Gy (1.8 Gy/day in 28 fractions) over 5.5 weeks, plus 5-fluorouracil (425 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GLUT1, LDH5, PDK1, and HIF-1α proteins was determined by immunohistochemistry and was assessed in 104 patients with rectal cancer treated with neoadjuvant chemoradiotherapy. RESULTS: This study included stage II and III rectal cancer patients, and each stage accounted for each 50 % of the total cases. A high expression of GLUT1 protein was associated with a significantly lower rate of ypCR compared with low expression of GLUT1 protein (4.0 % vs. 27.8 %, respectively; p = 0.012). GLUT1 expression was also significantly higher in the poor response group (Grade 0, 1) than in the good response group (Grade 2, 3) (34.0 % vs. 14.8 %, respectively; p = 0.022). In recurrence analysis, the expression of GLUT1 protein demonstrated a significant correlation with time to recurrence, based on a log-rank method (p = 0.016). When analyzed by multiple Cox regression, the positive expression of GLUT1 was the most significant and independent unfavorable prognostic factor (p = 0.004). CONCLUSIONS: GLUT1 expression is a predictive and prognostic factor for pathologic complete response and recurrence in rectal cancer patients treated with 5-flurouracil and leucovorin neo-adjuvant chemoradiotherapy.

Clinicopathological implications of the expression of hypoxia-related proteins in gastric cancer.

OBJECTIVES: Tumor hypoxia confers poor prognosis of a wide range of solid tumors due to increased malignancy, increased likelihood of metastasis and treatment resistance. The aim of this study was to assess the significance of the expression of HIF-1α and HIF-1α-inducible proteins in gastric cancer and their impact on prognosis. MATERIALS AND METHODS: The expression of HIF-1α, GLUT-1, CA-9, and iNOS proteins was analyzed by immunohistochemistry in 193 gastric adenocarcinomas (GAs) and 20 normal gastric mucosa. RESULTS: HIF-1α, GLUT-1, CA-9 and iNOS were expressed in 52.3%, 43.0%, 57.0%, and 43.0% of GAs, respectively, which are higher than the normal counterparts except for CA-9. HIF-1α expression was positively correlated with the expression of GLUT-1, CA-9 and iNOS. GLUT-1 expression was higher in the intestinal type (p = 0.012); however, iNOS expression was higher in the less-differentiated type and the diffuse type (p = 0.006, p = 0.032, respectively). The expression of HIF-1α and GLUT-1 was significantly correlated with lymph node metastasis (p = 0.009, p = 0.008, respectively), while the expression of GLUT-1 and iNOS was significantly correlated with the depth of invasion and advanced stage (p = 0.044, p = 0.004; p = 0.009, p = 0.008, respectively). Overall survival was shorter in patients with GLUT-1 expression than in those without GLUT-1 expression, which was statistically significant by univariate analysis (p = 0.042). On multivariate analysis, however, stage was determined as the only independent prognostic marker (p < 0.001). CONCLUSIONS: Our data suggest that overexpression of HIF-1α, GLUT-1, and iNOS may play an important role in gastric cancer progression. GLUT-1 is a potential candidate for predicting patient survival.

Reduced expression of TFF1 and increased expression of TFF3 in gastric cancer: correlation with clinicopathological parameters and prognosis.

OBJECTIVES: The trefoil factor family (TFF) is composed of three thermostable, and protease-resistant proteins, named TFF1, TFF2 and TFF3, and plays a role in gastrointestinal mucosal defence and repair. Recently, TFFs have been found to be related to the development of various types of cancer. This study assessed the relationship between the expression of TFF1 and TFF3 and the clinicopathological parameters in gastric carcinoma (GC). MATERIALS AND METHODS: The expression of TFF1 and TFF3 was analyzed by immunohistochemistry in 292 GCs and 20 normal gastric tissues. RESULTS: All normal gastric tissues expressed TFF1, but 53.8% of GCs showed reduced TFF1 expression. However, TFF3 was not detected in normal gastric tissues and 44.2% of GCs showed a high level of expression. Highly expressed TFF3 was significantly correlated with lymph node metastasis, lymphatic invasion, vein invasion, and advanced stage. The overall survival was shorter in patients with high expression of TFF3 than in those with low expression of TFF3 in 292 GCs and in 125 early GCs (EGCs). Moreover, in patients with EGCs, high expression of TFF3, associated with reduced expression of TFF1, was determined as an independent poor prognostic marker. CONCLUSIONS: Reduced expression of TFF1 and increased expression of TFF3 may play a role in the carcinogenesis of gastric cancer. Furthermore, high expression of TFF3 with reduced expression of TFF1 may be a marker of poor prognosis for patients with EGC.

Clinical Outcomes of Upfront Primary Tumor Resection in Synchronous Unresectable Metastatic Colorectal Cancer.

The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group (n = 42) showed better performance (p = 0.061), had higher frequencies of right-sided origin (p = 0.058), the T4 stage (p = 0.003), the M1a stage (p = 0.012), and <2 organ metastases (p = 0.002), and received fewer targeted agents (p = 0.011) than the chemotherapy group (n = 163). The PTR group showed a trend for longer OS (20.5 versus 16.0 months, p = 0.064) but was not related to OS in Cox regression multivariate analysis (p = 0.220). The male sex (p = 0.061), a good performance status (p = 0.078), the T3 stage (p = 0.060), the M1a stage (p = 0.042), <2 organ metastases (p = 0.035), an RAS wild tumor (p = 0.054), and the administration of targeted agents (p = 0.037), especially bevacizumab (p = 0.067), seemed to be related to PTR benefits. Upfront PTR could be considered beneficial in some subgroups, but these findings require larger studies to verify.

Tumor budding as a risk factor of lymph node metastasis in submucosal invasive T1 colorectal carcinoma: a retrospective study.

BACKGROUND: This study was designed to identify risk factors for lymph node metastasis of early stage colorectal cancer, which was confirmed to a carcinoma that invaded the submucosa after radical resection. METHODS: In total, 55 patients revealing submucosal invasive colorectal carcinoma on pathology who underwent curative radical resection at the Department of Surgery, St. Vincent's Hospital, The Catholic University of Korea from January 2007 to September 2010 were evaluated retrospectively. Tumor size, depth of submucosal invasion, histologic grade, lymphovascular invasion, tumor budding, and microacinar structure were reviewed by a single pathologist. Student t-test for continuous variables and Chi-square test for categorical variables were used for comparing the clinicopathological features between two groups (whether lymph node involvement existed or not). Continuous variables are expressed as the mean ± standard error while statistical significance is accepted at P < 0.05. RESULTS: The mean age of 55 patients (34 males and 21 females) was 61.2 ± 9.6 years (range, 43-83). Histologically, eight (14.5%) patients had metastatic lymph node. In the univariate analysis, tumor budding (P = 0.047) was the only factor that was significantly associated with lymph node metastasis. Also, the tumor budding had a sensitivity of 83.3%, a specificity of 60.5%, and a negative predictive value of 0.958 for lymph node metastasis in submucosal invasive T1 colorectal cancer. CONCLUSIONS: The tumor budding seems to have a high sensitivity (83.3%), acceptable specificity (60.5%), and a high negative predictive value (0.958). A close examination of pathologic finding including tumor budding should be performed in order to manage early CRC properly.

Pathologic Implications of Radial Resection Margin and Perineural Invasion to Adjuvant Chemotherapy after Preoperative Chemoradiotherapy and Surgery for Rectal Cancer: A Multi-Institutional and Case-Matched Control Study.

We assessed the exact role of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CRT) and surgery in rectal cancer patients with positive surgical margin or perineural invasion (PNI). This multi-institutional study included 1799 patients with rectal cancer at cT3-4N0-2M0 stages. Patients were divided into two groups. The high-risk group had a positive margin and/or perineural invasion. The low-risk group showed no positive margin or PNI. Propensity-score matching analysis was performed, and a total of 928 patients, with 464 in each arm, were evaluated. The high-risk group showed significant differences in overall survival (OS, 73.4% vs. 53.9%, p < 0.01) and recurrence-free survival (RFS, 52.7% vs. 40.9%, p = 0.01) at five years between the adjuvant chemotherapy arm and observation arm. The low-risk group showed no significant differences in 5-year OS (p = 0.61) and RFS (p = 0.75) between the two arms. Multivariate analyses showed that age, pathologic N stage, and adjuvant chemotherapy were significantly correlated with OS and RFS in the high-risk group (all p < 0.05). Adjuvant chemotherapy improved OS and RFS more significantly in rectal cancer patients with positive surgical margin or PNI than in those with negative surgical margin and PNI.

The expression of claudin-1, claudin-2, claudin-3, and claudin-4 in gastric cancer tissue.

BACKGROUND: The claudins (CLDNs) are a family of functional tight junction proteins, and are involved with the epithelial-to-mesenchymal transition (EMT). The claudin proteins have a significant influence on the biological behavior of tumor progression in several types of cancers. In this study, we aimed to evaluate the expression pattern of claudin-1, claudin-2, claudin-3, and claudin-4 in gastric cancer tissue. MATERIALS AND METHODS: Tissue was obtained from surgically resected specimens of 72 patients who were diagnosed with gastric adenocarcinoma at a single institution. The expressions of claudin-1, claudin-2, claudin-3, and claudin-4 were determined by immunohistochemical staining with the ABC method. RESULTS: Claudin-2 demonstrated the highest expression rate (73.6%) and claudin-4 demonstrated the lowest expression rate (44.4%). The expression of claudin-1 was significantly lower in cases of intestinal type adenocarcinoma based on the Lauren classification. The expressions of claudin-3 and claudin-4 were significantly lower in cases with positive lymphatic invasion. The expression of claudin-3 was significantly lower in cases with an advanced T-stage (T3 and T4). The expression of claudin-3 showed significantly positive correlations with the expression of the other claudin proteins. In survival analysis, the expression of claudin-4 was related to good overall survival rate with significance (P = 0.046). CONCLUSION: We suggest that claudin-3 and claudin-4 represent useful molecular markers for gastric cancer. Claudin-3 and claudin-4 would be the most important proteins related to the lymphatic invasion process, and claudin-4 would be useful with prognostic marker based on our results. Further investigations with a greater number of subjects are required to identify the action mechanism of claudin in gastric cancer.

Risk factors in malignant transformation of gastric epithelial neoplasia categorized by the revised Vienna classification: endoscopic, pathological, and immunophenotypic features.

BACKGROUND: According to the revised Vienna classification, the surgical removal of gastric epithelial neoplasia category 3 (low-grade dysplasia) lesions is not necessary, whereas the removal of category 4 lesions (high-grade dysplasia and intramucosal cancer) is obligatory. However, approximately 15%-30% of low-grade adenomas/dysplasia progress to high-grade lesions or adenocarcinoma, and it is difficult to determine which lesions will advance to true malignancy. The aim of this study was to evaluate the endoscopic, pathological, and immunophenotypic differences between category 3 and 4 lesions according to the revised Vienna classification. METHODS: All tissue samples were excised by endoscopic mucosal resection. Fifty-two category 3 tissue samples and 54 category 4 samples were evaluated by endoscopic findings; by pathology examination of the surrounding mucosa; and by CD10, MUC2, MUC5AC, MUC6, and RUNX3 immunohistochemical staining. RESULTS: Univariate analysis showed that the size of the lesion, color change, ulceration, gastritis score of the surrounding mucosa, and positive expression of MUC6 were associated with category 4 lesions. Multivariate analysis showed that the size of the lesion, ulceration, and positive expression of MUC6 were strongly associated with category 4 lesions. CONCLUSION: Lesions more than 17 mm in diameter or lesions that are associated with ulceration have the potential for malignant transformation. Positive immunoreactivity for MUC6 appears to be a complementary marker for malignant transformation of gastric epithelial neoplasia.

The detection of Helicobacter pylori cag pathogenicity islands (PAIs) and expression of matrix metalloproteinase-7 (MMP-7) in gastric epithelial dysplasia and intramucosal cancer.

BACKGROUND: The cag pathogenicity island (PAI), a Helicobacter pylori virulence factor, is associated with the pathogenesis of gastric cancer. Matrix metalloproteinase-7(MMP-7) is upregulated in the epithelial cells of gastric cancer. To date, there is limited information available on the role of cag PAI and MMP-7 in precursor lesions. In this study, we aimed to identify virulent H. pylori strains and the expression of MMP-7 in samples of gastric epithelial dysplasia and intramucosal cancer. METHODS: One hundred and twelve tissues excised by endoscopic mucosal resection, 76 specimens with gastric epithelial dysplasia and 36 with intramucosal cancer, were examined. All tissue samples were paired with surrounding normal epithelial tissue samples. We performed polymerase chain reaction for cagA and cagL in neoplasia and paired normal specimens, and assessed the matrix metalloproteinase (MMP)-7 expression by immunohistochemical staining. RESULTS: There was a significant difference in the frequencies of cagA or cagL between specimens with gastric dysplasia and those with intramucosal cancer. We confirmed greater expression of MMP-7 immunoreactivity in intramucosal cancers infected with a virulent H. pylori strain. CONCLUSION: Our results suggest that infection with a virulent H. pylori strain was associated with early-stage gastric cancer and that carcinogenesis was associated with cag PAI-dependent MMP-7 upregulation.

Acute thermal injury of the esophagus from solid food: clinical course and endoscopic findings.

A 53-yr-old man presented with a two-day history of odynophagia and a foreign body sensation. Two days before admission, the patient began to experience odynophagia and a foreign body sensation in the chest after swallowing several extremely hot pieces of solid food (prawn) in haste. Endoscopy revealed a huge longitudinal ulcer, typical of friable hyperemic mucosa with necrotic debris along the full length of the esophagus in the posterolateral region. Here we present the clinical course of serial endoscopy of an acute thermal injury of the esophagus caused by solid food.

Galactography acquired with digital mammography in patients with nipple discharge: a retrospective analysis.

PURPOSE: To evaluate the galactographic findings taken with digital mammography and to compare the findings between benign and malignant breast diseases. MATERIALS AND METHODS: Galactographic findings were retrospectively analyzed and compared with histopathological results for 42 patients who showed abnormal findings on galactography and had histologically proven diagnoses between January 2005 and March 2008. A galactography was acquired using full-field digital mammography (Hologic Lorad Selenia; Danbury, USA). The difference in galactographic findings between malignant and benign breast diseases was analyzed using chi(2) test. A value of P < 0.05 was considered statistically significant. RESULTS: Of the total 42 cases, 11 cases were malignant breast diseases and 31 were benign diseases. Common galactographic findings of benign diseases include ductal obstruction (48.3%) and single filling defect (51.6%), and common findings for malignant tumor include ductal dilatation (72.7%) and stenosis (63.6%). Ductal stenosis, microcalcifications or mass adjacent to abnormal duct, multiple filling defects, ductal wall irregularity, ductal distortion and irregular filling defects were more prevalently seen in malignant cases. A single filling defect and lobular filling defect was more prevalently seen in benign cases (P < 0.05). Ductal dilatation was a common finding in both malignant and benign cases with no significant difference. CONCLUSIONS: Ductal lesions were well visualized on galactography acquired with a digital mammography. A preoperative diagnostic galactography is useful in making a differential diagnosis between benign diseases and malignant tumors in patients with pathologic nipple discharge.

Expression patterns of programmed death-1 and programmed death-1 ligand-1 on T cells in gastric cancer.

The aim of the present study was to evaluate programmed death-1 (PD-1) and programmed death-1 ligand-1 (PD-L1) expression in gastric carcinoma and to assess their effect on survival rate. A total of 170 surgically resected specimens were obtained from patients diagnosed with gastric carcinoma at St. Vincents Hospital, The Catholic University of Korea. Paraffin tissue sections from tissue microarray blocks were subjected to immunohistochemical analysis of PD-1 and PD-L1. In addition, PD-1 expression on CD4+ and CD8+ T cells isolated from peripheral blood mononuclear cells and gastric cancer tissues was evaluated by multicolor flow cytometry. PD-1 and PD-L1 were expressed in 30.0 and 60.5% of the gastric cancer tissues, respectively. The expression of PD-L1 was higher in patients with advanced T (P=0.035) and Tumor, Node and Metastasis stage (P=0.05). The patients with positive PD-L1 expression had shorter disease-free survival time than those without PD-L1 expression (P=0.005). Additionally, PD-L1 expression was significantly associated with poor prognosis (P=0.015). PD-1 and PD-L1 expression levels were significantly higher on CD8+ T cells than on CD4+ T cells (P<0.001). The data of the present study suggested that PD-L1 expression may be an independent indicator of poor prognosis in patients with gastric cancer. Furthermore, PD-L1 expression may play a role in immune evasion of gastric cancer.

Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer.

BACKGROUND: Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear. METHODS: We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed. RESULTS: Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II-IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I-positive tumors than in HLA-I-negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort. CONCLUSIONS: Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

Significance of perineural and lymphovascular invasion in locally advanced rectal cancer treated by preoperative chemoradiotherapy and radical surgery: Can perineural invasion be an indication of adjuvant chemotherapy?

PURPOSE: To investigate the prognostic significance of lymphovascular space invasion (LVI) and perineural invasion (PNI) in rectal cancer. METHODS AND MATERIALS: Clinical data of 1,232 stage II-III rectal cancer patients from six tertiary institutions were analyzed. All patients were treated by long-course preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Adjuvant systemic chemotherapy was performed for 962 (78.1%) patients according to the multidisciplinary team's decision. Treatment outcomes and prognostic factors were evaluated according to the lymphovascular invasion (LVI) and perineural invasion (PNI) status. RESULTS: Five-year overall survival (OS) and recurrence-free survival (RFS) rates of the entire cohort were 84.1% and 71.1%, respectively. There is a significant difference in 5-year OS among both-absent, LVI+ only, PNI+ only, and both-present groups (89.1% vs. 77.9% vs. 67.6% vs. 56.2%; p < 0.001). RFS at five years was significantly different among both-absent, LVI+ only, PNI+ only, and both-present groups (78.7% vs. 58.7% vs. 44.6% vs. 38.6%; p < 0.001). The 5-year distant failure-free survival (DFFS) rate was also significantly different among four groups (84.6% vs. 61.4% vs. 54.2% vs 48.6%; p < 0.001). Although adjuvant chemotherapy did not affect 5-year DFFS in the entire cohort, adjuvant chemotherapy significantly reduced the distant failure rate in patients with PNI+ patients (44.9% vs. 54.6%, p = 0.048), not LVI+ patients (65.0% vs. 56.1%, p = 0.487). CONCLUSION: Compared to LVI, PNI is a more significant prognostic factor in stage II-III rectal patients treated by preoperative CRT and TME surgery. The status of PNI rather than LVI could be an indicator for identifying patients who could benefit from adjuvant systemic chemotherapy.