Bigger Tumor Size Research Articles

Prognostic significance of bladder neck involvement in non-muscle-invasive bladder cancer: A SEER database analysis with 19,919 patients.

PurposeTo study prognostic values of bladder neck involvement (BNI) and survival outcomes in non‐muscle‐invasive bladder cancer (NMIBC).Method and materialsThe national Surveillance, Epidemiology, and End Results database (2004–2015) was applied to gain further insight into the prognostic values of BNI and 19,919 patients diagnosed with NMIBC were included in our study. We used the Kaplan–Meier method with the log‐rank test and subgroup analyses to evaluate cancer‐specific survival (CSS) and overall survival (OS). In addition, the multivariable Cox proportional hazard model and propensity score matching (PSM) were utilized.ResultsIn all, 3446 patients with BNI and 16,473 patients with sites except for bladder neck were enrolled in our study. Compared with other sites, a tendency toward a higher proportion of higher grade (p < 0.001), bigger tumor size (p < 0.001), and more patients with T1 and Tis stage (p < 0.001) was seen in BNI group. After 1:1 PSM, 3425 matched pairs were selected. Under the survival analyses, the BNI group had a lower survival probability in both OS (p = 0.0056) and CSS analyses (p < 0.0001) in NMIBC patients. However, in the subgroup analysis, only observed in the Ta and T1 stage in terms of CSS (all p < 0.05), and patients with Tis stage failed to show statistical survival differences (p > 0.05). In addition, subgroups stratified by tumor size and grade all revealed poor prognosis of BNI in NMIBC patients. Moreover, better survival outcomes of OS were observed in BNI patients who received radical cystectomy (p = 0.02) or chemotherapy (p < 0.001) multivariable Cox regression after PSM revealed that the BNI group had a higher risk of overall mortality (OM) (BNI vs. other sites hazards ratios [HR]: 1.127, 95% CI: 1.154–1.437, p < 0.001) and cancer‐specific mortality (CSM) (BNI vs. other sites HR: 1.127, 95% CI: 1.039–1.223, p < 0.001), while before PSM, similar situations were only existed in CSM (BNI vs. other sites HR: 1.288, 95% CI: 1.154–1.437, p < 0.001).ConclusionsThe prognosis of BNI was poorer than that of the other sites. BNI was an independent risk factor for OM and CSM in patients with NMIBC, especially for those with Ta or T1 stage.

Occurrence of residual disease in specimens of re‐excision surgery in patients with positive margins of primary quadrantectomy

Performing a re-intervention following a positive margin after primary lumpectomy in patients with breast cancer entails several disadvantages such as additional costs and postponing the follow-up treatments. In the present study, we sought to measure the incidence rate of residual disease in specimens taken from breast cancer patients who had positive margins after quadrantectomy and also compare the clinical and pathological factors between patients with and without a residual disease after the secondary surgery. All of the medical records of patients undergoing quadrantectomy from December 1994 to December 2019 were collected from Shiraz Breast Cancer Registry (SBCR). Patients were divided into two subgroups of patients with and without residual disease from the secondary surgery and also with and without positive margin from the first operation. Two groups were compared in terms of all clinicopathological factors. The records of 4843 patients undergoing quadrantectomy were reviewed, of which 132 (2.3%) had involved margins. Of these, 112 patients underwent a secondary surgery and 28 had residual disease (25%). No clinicopathological factor was correlated with presence of residual cancer. Also, bigger tumor size (p<0.001) and the presence of in situ component (p<0.001) were associated with positive margin and hence the need for a re-excision surgery. These results revealed that the significant rate of residual disease in the specimens of the secondary surgery indicates that a re-operation (either re-excision or simple mastectomy) cannot be omitted after obtaining a positive margin from the primary quadrantectomy.

Clinical implication of tumor location in intrahepatic cholangiocarcinoma and assessment of the current staging system

Intrahepatic cholangiocarcinoma (ICC) exhibits a variety of morphologic and histologic growth pattern, and its treatment and prognosis are known to vary depending on the location and extent of tumor. This study aims to compare the clinical data according to the tumor location in ICC and to verify the current staging system used in ICC. 302 patients who underwent curative resection were reviewed. Central type ICC (C-ICC) was defined when the tumor had an invasion of intrahepatic secondary confluence or segmental branches of the bile duct and peripheral type ICC (P-ICC) when the tumor was located more peripherally. Clinicopathologic characteristics, oncological outcomes, and prognostic stratification of the AJCC 8th staging system were assessed. Among 302 patients, 123 were classified as C-ICC and 179 as P-ICC. Bigger tumor size, higher rate of elevated CA19-9 level, vascular invasion, periductal invasion type, R1 rate, and advanced T stage was found in C-ICC. Five-year overall survival rates were 34.0% for C-ICC and 47.5% for P-ICC (p = 0.005). A significant difference in disease-free survival was seen as well (p = 0.036). The prognostic utility of ICC T stage was assessed in N0 C-ICC but failed to stratify T2, T3, and T4 tumors (median survival; T2: 37 m. T3: 34 m. T4: 33 m. p = 0.591). When applying the perihilar cholangiocarcinoma staging system (p < 0.001), stratification was improved and similar results were also seen in the overall staging. C-ICC has a worse aggressive clinical course compared to P-ICC. The perihilar cholangiocarcinoma cancer staging system is better than ICC staging to stratify the prognosis of C-ICC.

Risk factors and impact of unplanned conversion during laparoscopic hepatectomy on oncologic outcomes in patients with hepatocellular carcinoma

This study aimed (1) to compare the perioperative and oncologic outcomes of laparoscopic (Lap), unplanned open conversion (Conversion) and planned open (Open) liver resection for hepatocellular carcinoma (HCC) located in the anterolateral segments of the liver and (2) to identify the risk factors for unplanned open conversion. We retrospectively reviewed the data of 374 patients who underwent liver resection for HCC located in anterolateral segments between 2004 and 2018. All patients were divided into three groups for analysis: Lap (N = 299), Open (N = 62) or Conversion (N = 13). Compared to Lap group, Conversion group showed longer operation time (300.00 ± 142.08 vs 182.03 ± 105.65 min, p = 0.000), greater blood loss (1,596.15 ± 1,604.87 vs. 411.35 ± 614.33 mL, p = 0.021) with higher transfusion rate (23.1% vs. 5.4%, p = 0.009), higher postoperative complication rate (38.5% vs. 12.4%, p = 0.008), longer hospital stay (10.38 ± 5.69 vs. 6.48 ± 7.71 days, p = 0.040). Moreover, Conversion group showed lower R0 resection rate (84.6% vs. 96%, p = 0.000) and higher early tumor recurrence rate (61.5% vs. 23.7%, p = 0.008). Even in comparison with Open group, Conversion group showed longer operation time (300.00 ± 142.08 vs 222.42 ± 88.10 min, p = 0.012) and greater blood loss (1,596.15 ± 1,604.87 vs. 812.50 ± 977.66 mL, p = 0.024). Risk factors for unplanned conversion to open were analyzed as bigger tumor size (OR 1.35, 95% CI 1.05-1.74, p = 0.020), multiple tumor (OR 5.95, 95% CI 1.45-24.39, p = 0.013), and other organ invasion (OR 15.32, 95% CI 1.80-130.59, p = 0.013). Unplanned open conversion showed poor perioperative and oncologic outcomes compared to laparoscopy and planned open hepatectomy. Therefore, planned open liver resection should be recommended for HCCs located in anterolateral liver segments.

LncRNA AWPPH as a prognostic predictor in human cancers in Chinese population: evidence from meta-analysis.

Background: Long non-coding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is dysregulated in a variety of human cancers. However, the prognostic value of AWPPH in various cancers remains unclear.Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR = 1.79, 95%CI: 1.44–2.14, P<0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR = 2.50, 95%CI: 1.94–3.22, P<0.001), bigger tumor size (OR = 2.64, 95%CI: 1.47–4.73, P=0.001), macro-vascular invasion (OR = 2.08, 95%CI: 1.04–4.16, P=0.04) and lymph node metastasis (OR = 2.68, 95%CI: 1.82–3.96, P<0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding.Conclusions: Up-regulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers among the Chinese population.

Knockdown of NOLC1 Inhibits PI3K-AKT Pathway to Improve the Poor Prognosis of Esophageal Carcinoma.

Objective Esophageal carcinoma (ESCA) is a common malignant gastrointestinal tumor. The abnormal expression of NOLC1 is involved in the tumorigenesis of various human tumors, whereas the function and mechanism of NOLC1 in ESCA remain unclear. In this study, we explored the relationship between NOLC1 and poor prognosis of ESCA, and its role and mechanism in the occurrence of ESCA. Methods The NOLC1 expression in ESCA tissues and cell lines was determined by qRT-PCR, immunohistochemistry, or western blot. The Kaplan–Meier method was conducted to estimate the overall survival. Cox regression analysis was carried out to examine the association between patient characteristics and prognosis. A recombined lentiviral vector containing NOLC1 was applied for transfecting ESCA cells (Eca109 and TE-13) and established a stable cell line with low NOLC1 expression or high NOLC1 expression, in the absence or presence of PI3K inhibitor (LY294002) treatment. Cell proliferation, apoptosis rate, invasion ability, migration ability, and PI3K/AKT pathway were detected by CCK8 assay, flow cytometry, Transwell assay, wound-healing assay, and western blot. Results NOLC1 overexpression was observed in ESCA tissues and ESCA cell lines (EC9706, Eca109, TE-13, Kyse170, T.TN) compared with adjacent normal tissues and normal esophageal cell line HEEC. NOLC1 overexpression was markedly associated with bigger tumor size, lymph node metastasis, and advanced TNM stage. Patients with NOLC1 overexpression have shorter overall survival than that of those with low NOLC1 expression. NOLC1 overexpression was considered to be an independent poor prognostic factor affecting overall survival. NOLC1 knockdown inhibited proliferation, migration, invasion, and cyclin B1 expression and promoted the apoptosis and cleaved-caspase-3 expression of Eca109 and TE-13 cells. NOLC1 overexpression accelerated proliferation, migration, invasion, and cyclin B1 expression and inhibited the apoptosis and cleaved-caspase-3 expression of ESCA cells via activating PI3K/AKT pathway. Rescue experiments showed that PI3K inhibitor (LY294002) could reverse the phenomenon caused by NOLC1 overexpression. Conclusion NOLC1 may be a marker for poor prognosis. It can participate in the occurrence and development of ESCA via the PI3K/AKT pathway.

Decreased Expression of MPC2 Contributes to Aerobic Glycolysis and Colorectal Cancer Proliferation by Activating mTOR Pathway.

Mitochondrial Pyruvate Carrier 1 (MPC1), one of the rate-limiting proteins involved in glycolysis metabolism, has been demonstrated as a tumor inhibitor in several cancers. This study was conducted with the aim of exploring the role and underlying mechanisms of MPC2 in colorectal cancer (CRC). Here, we found that MPC2 expression was decreased in CRC samples. According to the analysis on our TMA data, lower expression of MPC2 is correlated with a higher incidence of distant metastasis and lymph node invasion, bigger tumor size, low survival rate of patients, and advanced T stages. Functionally, in vivo/vitro experiments showed that MPC2 knockdown induced CRC cell proliferation and growth, while MPC2 overexpression inhibited the proliferation and growth of CRC. Further study demonstrated that MPC2 knockdown resulted in aerobic glycolysis in CRC cells. Similarly, MPC2 overexpression in CRC cells also caused inhibited aerobic glycolysis. Further study found that MPC2 knockdown in CRC cell lines activated the mTOR signaling pathway, and the addition of rapamycin reversed the promoting effect of MPC2 knockdown on CRC proliferation and glycolysis. Likewise, the addition of MHY1485 also reversed the MPC2 overexpression's role in hindering aerobic glycolysis in CRC cells. Collectively, our study established that low expression of MPC2 led to CRC growth as well as aerobic glycolysis through the regulation of the mTOR pathway in CRC cells, indicating a potential biomarker and therapy target for CRC.

Factors associated with epiphora following orbital-sparing maxillectomy via modified Weber-Ferguson incision with lower blepharoplasty.

The aims of the study were to estimate the frequency of epiphora and to identify factors associated with epiphora after orbital-sparing maxillectomy via modified Weber-Ferguson incision with lower blepharoplasty (OSOSM-MWFILB). We performed a retrospective cohort study enrolling a sample derived from the patient population undergoing OSM-MWFILB over a 7-year period. The predictor variables were grouped into demographic, related health status, anatomic, tumor-specific, and therapeutic categories. The primary outcome variable was the presence of postmaxillectomy epiphora (PME). Descriptive, univariate, and multivariate regression mixed-effect models were computed. The study sample was composed of 134 patients (46.3% females; 71.6% squamous cell carcinomas) with a mean age of 64.7 ± 12.2 years. There were 23 (17.2%) PME events, which were significantly associated with eight variables: male gender, poor general health (ASA III-IV), large vertical defect (Brown and Shaw's class III-IV), squamous cell carcinoma tumor type, big tumor size (T3-4), cervical lymph node metastasis (N1-2), long operating time > 3 h, and adjuvant radio(chemo)therapy in both univariate mixed regression and multivariate Cox hazards analyses. Healing of PME in irradiated patients was significantly delayed. Ophthalmologic consequences in patients undergoing OSM-MWFILB require particular attention, especially in case of advanced tumors, multiple comorbidities, or long surgery with postoperative radio(chemo)therapy. This emphasizes the importance of appropriate cooperation between the surgeons and ophthalmic colleagues.

The Prognostic Values of PARP-1 Expression in Uveal Melanoma.

Background: Uveal melanoma is the most common primary intraocular malignancy in adults. In advanced cases, the prognosis is very poor. Thus far, no effective methods of pharmacotherapy of this cancer have been found. The aim of the study was to evaluate the expression of PARP-1, the best-known member of the family of poly(ADP-ribose) polymerases, in uveal melanoma and its associations with clinicopathological parameters, overall survival, and disease-free survival. Methods: The study included 91 patients who underwent enucleation due to uveal melanoma. PARP-1 expression was assessed by immunohistochemistry. Results: High PARP-1 expression was associated with more frequent chromosome 3 loss, higher histopathological grade, bigger tumor size, and absence of intrascleral extension. High PARP-1 expression was associated with shorter overall survival time and disease-free survival time. Conclusions: The above findings indicate that high expression of PARP-1 can be considered as an unfavorable prognostic factor in uveal melanoma.

Higher tumor protein kinase D1 correlates with increased tumor size, BCLC stage, CA199 level, AFP level and worse overall survival in hepatocellular carcinoma patients

ObjectiveHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Protein kinase D1 (PKD1) is recognized as a key regulator in the progression in several solid cancers, while its clinical role in HCC is unclear. This study aimed to evaluate the correlation of PKD1 with clinical features and prognosis in HCC patients. MethodsA total of 218 HCC patients who underwent resection were retrospectively enrolled. PKD1 expression in tumor (N = 218) and adjacent (N = 110) tissues was detected by immunohistochemical staining, scored by a semi-quantitative scoring method ranging from 0 to 12, and further classified as PKD1-, PKD1+, PKD1++ and PKD1+++ for analysis. Meanwhile, patients’ clinical features and survival data were acquired from the database. ResultsPKD1 was elevated in tumor tissues compared with adjacent tissues. Meanwhile, higher tumor PKD1 was correlated with elevated tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, carbohydrate antigen 199 (CA199) level and alpha fetoprotein (AFP) level; while no correlation was found in tumor PKD1 with patients’ basic features or liver function indexes. Moreover, higher tumor PKD1 was correlated with worse overall survival (OS) in HCC patients, then further validated as an independent predictive factor for worse OS by multivariate Cox’s regression model analysis. Additionally, in Child-Pugh stage A, Child-Pugh stage B, BCLC stage 0/A, and BCLC stage B subgroups, higher tumor PKD1 was also correlated with worse OS. ConclusionHigher PKD1 in tumor tissues correlates with elevated BCLC stage, bigger tumor size, increased CA199 level, higher AFP level and worse OS in HCC patients.

The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles.

Background and aims: Long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is aberrantly expressed in various cancers and associated with cancer progression. A comprehensive meta-analysis was performed based on published literature and data in the Gene Expression Omnibus database, and then the Cancer Genome Atlas (TCGA) dataset was used to assess the clinicopathological and prognostic value of FOXD2-AS1 in cancer patients.Methods: Gene Expression Omnibus databases of microarray data and published articles were used for meta-analysis, and TCGA dataset was also explored using the GEPIA analysis program. Hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the role of FOXD2-AS1 in cancers.Results: This meta-analysis included 21 studies with 2391 patients and 25 GEO datasets with 3311 patients. The pooled HRs suggested that highly expressed FOXD2-AS1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS). Similar results were obtained by analysis of TCGA data for 9502 patients. The pooled results also indicated that FOXD2-AS1 expression was associated with bigger tumor size and advanced TNM stage, but was not related to age, gender, differentiation and lymph node metastasis.Conclusion: The present study demonstrated that FOXD2-AS1 is closely related to tumor size and TNM stage. Additionally, increased FOXD2-AS1 was a risk factor of OS and DFS in cancer patients, suggesting FOXD2-AS1 may be a potential biomarker in human cancers.

Risk factors for conversion to thoracotomy from video-assisted thoracoscopic surgery of lung cancer

ObjectivesIntraoperative conversion to thoracotomy from video-assisted thoracoscopic surgery (VATS) is associated with increased adverse events, which is a major concern. We aim to explore the related risk factors in lung cancer patients. MethodsIn our study, the data from 1305 patients who underwent VATS between June 2017 and May 2020 were retrospectively collected, among which 67 patients underwent unexpected conversion to thoracotomy. All patients were divided into Non-conversion Group or Conversion Group according to whether they required a conversion to thoracotomy and the risk factors were explored by univariate and multivariate analyses. ResultsThe most common cause of conversion was fibrocalcified lymph nodes, found in 33 patients (49.3%). Multivariable logistic regression analysis demonstrates that the independent risk factors for the conversion were age ≥65 y (OR = 2.696, 95% CI: 1.487–4.887, p = 0.001), tumor size >3 cm (OR = 4.527, 95% CI: 2.490–8.233, p < 0.001), and tumor location in the left upper lung (OR = 3.809, 95% CI: 1.737–5.492, p < 0.001). ConclusionsAdvanced age, bigger tumor size and tumor at the left upper lobe could lead to conversion. In the early VATS learning cases, surgeons should try to choose patients with lower risk of conversion to thoracotomy.

Combining the Fibrinogen-to-Pre-Albumin Ratio and Prognostic Nutritional Index (FPR-PNI) Predicts the Survival in Elderly Gastric Cancer Patients After Gastrectomy.

BackgroundInflammation and nutrition are important causes contributing to the progression and poor survival of gastric cancer (GC). The objective of this study is to investigate the prognostic significance of the preoperative fibrinogen-to-pre-albumin ratio (FPR) and the prognostic nutritional index (PNI) in GC patients who have undergone gastrectomy.MethodsA total of 274 patients with resected pathological GC from January 2007 to December 2013 were enrolled in this retrospective study. Survival analysis was performed using Kaplan–Meier and log rank tests. Univariate and multivariate analyses were established to identify independent prognostic factors of 5-year survival. A predictive nomogram was used to predict prognosis of overall survival (OS), and its accuracy was determined by Harrell’s concordance index (C index).ResultsA high preoperative FPR-PNI score was significantly correlated with age, bigger tumor size, more lymphatic metastases and advanced TNM stage. Univariate analysis revealed that the GC patients with high FPR, low PNI and high FPR-PNI scores had shorter survival time. Multivariate analysis showed that FPR-PNI was an independent prognostic factor for OS in GC patients, especially in elderly patients. In the sub-analysis by age, the FPR-PNI score could significantly increase the accuracy of prognosis compared with the FPR and PNI alone in elderly GC patients.ConclusionThe preoperative FPR-PNI score is an effective independent prognostic index for GC patients after surgery, especially in elderly patients.

MON-324 Management and Therapeutic Response Comparison in Prolactinomas According to Tumor Size

Prolactinomas are the most common type of functioning pituitary adenomas and up to 50% of all adenomas in clinical practice. Prolactinomas are more prevalent in women; nonetheless, they may occur at any age and in both genders, and represent the most common cause non-physiological hyperprolactinemia. Prolactin-secreting adenomas are classified by their tumor size as follows: microprolactinomas (<1 cm), macroprolactinomas (>1cm) and giant prolactinomas (>4 cm). The clinical presentation of these tumors might differ from age, sex and size. Dopamine agonists, such as cabergoline or bromocriptine, have become the first line of treatment, since these agents decrease tumor size and prolactin (PRL) secretion. In Mexico, recent studies have focused on giant prolactinomas but there is missing data of the clinical and biochemical manifestations of the tumor size-effect within the three types of prolactinomas in our population. Objective: To determine the effect of the tumor size in the clinical and biochemical presentation, and the follow up in prolactinomas. Methods: This an observational, retrospective, retrolective study. Results: Patients were classified according to their tumor size and 489 patients with confirmed diagnosis of prolactinoma were included. The mean age was 36+-12 years old and 86% were women. The size was different among sex with 14 (2.9%) and 259 (52.9%) patients with microprolactinoma and 34 (6.9) and 152 (31.1%) with macroprolactinoma in men and women, respectively (p <0.001). The median PRL levels were higher among patients with bigger tumors, 115 (97-150) ng/mL for microprolactinomas, 219 (115-777) ng/mL for macroprolactinomas and 2000 (154-4000) ng/m for giant prolactinomas (p <0.001). Clinically, hypogonadism was more prevalent in women with bigger tumor size (p <0.001), as well as visual defects (p <0.001) and headache (p 0.008). Conclusion: The tumor size of prolactinomas affects the clinical and biochemical presentation as well as the years of follow up required.

Quantitative stain-free imaging and digital profiling of collagen structure reveal diverse survival of triple negative breast cancer patients

BackgroundStromal and collagen biology has a significant impact on tumorigenesis and metastasis. Collagen is a major structural extracellular matrix component in breast cancer, but its role in cancer progression is the subject of historical debate. Collagen may represent a protective layer that prevents cancer cell migration, while increased stromal collagen has been demonstrated to facilitate breast cancer metastasis.MethodsStromal remodeling is characterized by collagen fiber restructuring and realignment in stromal and tumoral areas. The patients in our study were diagnosed with triple-negative breast cancer in Singapore General Hospital from 2003 to 2015. We designed novel image processing and quantification pipelines to profile collagen structures using numerical imaging parameters. Our solution differentiated the collagen into two distinct modes: aggregated thick collagen (ATC) and dispersed thin collagen (DTC).ResultsExtracted parameters were significantly associated with bigger tumor size and DCIS association. Of numerical parameters, ATC collagen fiber density (CFD) and DTC collagen fiber length (CFL) were of significant prognostic value for disease-free survival and overall survival for the TNBC patient cohort. Using these two parameters, we built a predictive model to stratify the patients into four groups.ConclusionsOur study provides a novel insight for the quantitation of collagen in the tumor microenvironment and will help predict clinical outcomes for TNBC patients. The identified collagen parameters, ATC CFD and DTC CFL, represent a new direction for clinical prognosis and precision medicine. We also compared our result with benign samples and DICS samples to get novel insight about the TNBC heterogeneity. The improved understanding of collagen compartment of TNBC may provide insights into novel targets for better patient stratification and treatment.

Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing.

BackgroundPartner and localizer BRCA2 (PALB2) is a breast cancer predisposition gene, but the clinical relevance of PALB2 germline mutations in Chinese patients with breast cancer remains unknown. This study attempted to investigate the full prevalence and spectrum of PALB2 germline mutations in China and the associations between PALB2 germline mutations and breast cancer risk.MethodsA total of 21,216 unselected patients with breast cancer were enrolled from 10 provinces in China, and 5890 Chinese women without cancer were enrolled as healthy controls. PALB2 screening was based on next‐generation sequencing.ResultsA total of 16,501 BRCA1/2‐negative patients with breast cancer were analyzed. Deleterious PALB2 mutation carriers accounted for 0.97% (n = 160) in the breast cancer cohort and for 0.19% (n = 11) in the healthy control cohort. Forty‐one novel PALB2 germline mutations were identified. A high frequency of PALB2 c.751C>T was detected, and it accounted for 10.63% of the PALB2 germline mutations detected (17 of 160). PALB2 mutations were significantly associated with increased breast cancer risk (odds ratio [OR], 5.23; 95% confidence interval [CI], 2.84‐9.65; P < .0001), especially among women 30 years old or younger (OR, 10.09; 95% CI, 3.95‐25.79; P < .0001). Clinical characteristics, including a family history, bigger tumor size, triple‐negative breast cancer, positive lymph nodes, and bilateral breast cancer, were closely related to PALB2 mutations.ConclusionsThis study revealed a comprehensive spectrum of PALB2 germline mutations and characteristics of PALB2‐related breast cancer in China. PALB2 germline mutations confer a moderately increased risk for breast cancer but profoundly increase breast cancer risk for those 30 years old or younger in the Chinese population.

The prognostic value of lymph nodes mRNA CXCL12 expression in the breast cancer

Prognosis of breast carcinoma is influenced by age, tumor size, histological grade and type, lymph node status, as well as metastasic status. Chemokine receptor CXCR-4 with its ligand, CXCL-12, may play an important role in metastasis of breast carcinoma. However, the role of CXCL-12 mRNA as a prognostic factor and a therapeutic target of human breast cancer remains controversial. This study aimed to investigate the level of CXCL-12 mRNA expression in lymph nodes of patients with invasive ductal breast carcinoma and the difference within the prognostic factors. Axillary lymph nodes obtained from 50 cases of invasive ductal breast carcinoma, were divided into two groups, with and without lymph node metastasis. Each group consisted of 25 cases. Total RNA was extracted from formalin-fixed paraffin-embedded. The CXCL-12 mRNA expression was examined using qRT-PCR method. The mean differences between the two groups were analyzed using Mann-Whitney test. The differences between CXCL-12 mRNA expression and each prognostic factor ware analyzed using Mann-Whitney comparison test. CXCL-12 mRNA expression was significantly higher in the lymph node of patients with metastasis of breast carcinoma compared to the non-metastasis cases (p<0.01). There were significant differences between CXCL-12 mRNA expression with poorly histological grade (p=0.003), bigger primary tumor size (p=0.005) and age of ≥45 y.o (p=0.012) in the metastatic group, but there were no significant differences between both age of <45 and ≥45 y.o.This study suggests that the higher CXCL-12 mRNA expression level are associated with bigger tumor size and poor differentiation in breast cancer patient with lymph nodes metastasis

Male breast cancer: clinicopathological characterization of a National Danish cohort 1980\u20132009

BackgroundTo describe relevant pathological parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980 to 2009, and to relate these data to treatment, overall survival (OS) and standardized mortality rate (SMR).Materials and methodsThe MBCP cohort was defined from national Danish registers. A total of 643 MBCP were identified with tissue available in 457. Among these, 384 were primary operable. Where tissue blocks were available, tumor type, grade, estrogen receptor (ER), progesteron receptor (PgR) and androgen-receptor (AR) status as well as HER 2 and Ki67 were performed. OS was quantified by Kaplan–Meier estimates and SMR was calculated based on mortality rate among patients relative to the mortality rate in the general population.ResultsMale breast cancer was more often of ductal type, grade II and a very high proportion were ER and AR positive and HER2 negative. Intrinsic subtypes based on immunohistochemical evaluation showed luminal subtype. Ki67 ratio increased over period of study. OS declined by increased age, bigger tumor size, positive lymph node status, higher grade and Luminal B subtype. Hazard ratio and relative risk of SMR were highest for patients aged < 60 years.ConclusionMale breast cancer is of luminal subtype, but more often Luminal B. Ki67 is crucial in evaluation of subtypes by immunohistochemistry, but have limitations. Subtyping seems to be of major importance. AR also can have a role in future treatment.

118P - Association of metastatic disease with the original tumour size at presentation in colon cancer: A large population-based retrospective study

BackgroundThis study aimed to investigate the association of tumor size with the metastasis in colon cancer. MethodsPatients diagnosed with malignant colon cancer between January 1, 2010, and December 31, 2014, from the Surveillance, Epidemiology, and End Results (SEER) program were identified for the analysis. Patients with single metastatic colon cancer and tumor size measured in millimeters accurately were included in our study. ResultsA total of 97862 patients with malignant colon cancer were identified in the SEER database. The mean [stand deviation (SD)] tumor size of metastatic colon cancer was bigger than that of the nonmetastatic colon cancer (55.11 ± 35.62mm vs. 45.43±33.88 mm, P < 0.001). And our further analysis found that the mean [standard deviation(SD)] tumor sizes of liver metastasis, pulmonary metastasis, bone metastasis and brain metastasis were 55.20mm (36.08 mm), 55.09mm (30.47 mm), 46.72mm (34.07 mm) and 58.03mm (27.52 mm), respectively. ConclusionsColon cancer patients with bigger tumor size are associated with high risk of metastasis. Furthermore, tumor size of brain metastasis is bigger than that of liver and pulmonary metastasis, while bone metastasis is much smaller than that of liver and pulmonary metastasis. Legal entity responsible for the studyThe author. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.

A H. pylori-independent miR-21 overexpression in gastric cancer patients

BackgroundGastric cancer is the third leading cause of cancer-related death worldwide. miR-21 is one of the non-coding RNAs drastically deregulated in gastric cancer. However, the expression of miR-21 and its association with the clinicopathological characteristics of gastric cancer patients has not been studied clearly in Iranian population. ObjectivesWe aimed to analyze the expression level of miR-21 in a set of fresh gastric cancer specimens and healthy control samples. The expression level of miR-21 was then analyzed to explore for the statistically significant correlations with the clinicopathological features of the samples. MethodsmiR-21 expression level was quantitatively studied by RT-qPCR. The association studies between miR-21 expression and the clinical data were performed statistically. ResultsmiR-21 is highly expressed in gastric cancer patients regardless of H. pylori infection. This phenomenon significantly correlates with lymph node (p = 0.022) and peritoneal (p = 0.023) metastasis, stage I of gastric cancer (p = 0.021), greater curvature tumor location (p = 0.030) and bigger tumor size (p = 0.050) in gastric cancer patients in Iranian population. ConclusionmiR-21 is overexpressed in gastric cancer. This perturbation may not be mediated by H. pylori infection.