Frequency Of Node Metastasis Research Articles

Comprehensive analysis of clinicopathological characteristics in oral squamous cell carcinoma arising from oral submucous fibrosis: a retrospective study

BackgroundOral squamous cell carcinoma arising from oral submucous fibrosis is recognized as a clinicopathologically distinct disease. This study aims to summarize and compare the population and clinicopathologic characteristics of OSCC-OSF with other OSCC in Hunan Province, China. The objective is to formulate treatment strategies more in line with regional characteristics.MethodsA retrospective review of OSCC cases recruited from the Second Xiangya Hospital from 2010 to 2020 was conducted. A total of 1,413 OSCC patients were selected, including 481 patients with OSCC-OSF and 932 were other OSCC. Population characteristics, risk factors and clinicopathological manifestations were explored in OSCC-OSF and other OSCC, as well as thinprep cytologic test and DNA quantification.ResultsWe found that OSCC-OSF patients were younger than those with other OSCC. Both types of disease were predominantly observed in males compared to females. Tumor biopsy analysis indicated that tumor cells within OSCC-OSF patients were more likely to be well differentiated and showed a higher frequency of lymph node metastases. Clinicopathological factors, such as the chewing betel nuts habit and smoking, were more prevalent in OSCC-OSF patients in contrast to other OSCC. DNA quantification revealed that the number of DNA aneuploid cells was higher in OSCC-OSF compared to other OSCCs.ConclusionIn this study, OSCC-OSF is considered a clinicopathologically distinct disease. Compared with other OSCC, OSCC-OSF patients have a higher incidence of nodal metastases, an early clinical TNM stage, and a lower three-year survival rate. Therefore, early diagnosis and treatment are crucial to improving the prognosis of OSCC-OSF.

DICER1 Variants in Pediatric and Young Adult Thyroid Nodules.

Background: Recent studies have suggested that pathogenic variants of the DICER1 gene could be a driver of alterations in some pediatric thyroid nodules, but data are still limited. The aim of this study was to detect variants in the DICER1 gene in a large cohort of pediatric thyroid nodules and then correlate them with clinicopathological data, with a focus on the disease prognosis in patients with thyroid carcinoma. Methods: This retrospective cohort study consisted of 350 pediatric and young adult patients (aged 2-21 years) with thyroid nodules, from whom 275 fresh-frozen thyroid nodule samples and 92 fine-needle aspiration biopsy (FNAB) samples were collected. After an analysis of variants in major genetic alterations of thyroid tumors, variants in the DICER1 gene were identified using next-generation sequencing and multiplex ligation-dependent probe amplification methods. Peripheral blood was analyzed from patients with DICER1-positive tumors. The results of genetic analysis were then correlated with clinicopathological data. Results: Variants in the DICER1 gene were detected in a total of 24/350 (6.9%; 95%CI [4.4;10.0]) pediatric and young adult patients, respectively, in 10/119 (8.4%; [4.1;14.9]) patients with benign fresh-frozen tissue, in 8/141 (5.7%; [1.9;9.5]) with papillary thyroid carcinoma (PTC) and in 6/86 (7.0%; [4.1;14.6]) patients with FNAB. No other gene alteration was found in DICER1-positive samples. Germline DICER1 variants were identified in 11/24 (45.8%; [25.6;67.2]) patients. Two somatic (biallelic) variants in the DICER1 gene were found in 9/24 (37.5%; [18.8;59.4]) thyroid nodules. Somatic deletions of at least 3 Mbp long were revealed in 2/24 (8.3%; [1.0;27.0]) cases. DICER1-positive PTCs were significantly associated with the follicular subtype of PTC (p = 0.001), encapsulation (p = 0.006) and were larger in size (p = 0.035), but with no extrathyroidal extension (p = 0.039), and less frequent lymph node metastases (p = 0.003) compared with DICER1-negative PTCs. Patients with DICER1-positive PTC had an excellent response to treatment in 75% of cases. Conclusions: Variants of the DICER1 gene are frequently found in the thyroid nodules of pediatric and young adult patients. In our patients, DICER1-positive PTCs showed low invasiveness. Our findings support considering more conservative management for DICER1-positive low-risk PTCs.

How Can "No Specific Molecular Profile" Heterogeneity be Reduced in Molecularly Classified Endometrial Cancer?: Prognostic Significance of L1 Cell Adhesion Molecule.

This study aims to investigate the role of L1 cell adhesion molecule (L1CAM) in the prognostic assessment of endometrial cancers that have been depicted as having no specific molecular profile (NSMP) in molecular classification. This is a retrospective review of 150 patients who received the diagnosis of endometrial cancer and underwent surgery at the study center between January 2008 and January 2022. When evaluating L1CAM immunohistochemical staining, scoring was done according to the percentage of positivity in tumor cells. Accordingly, score 0 = 0%, score 1=1% to 10%, score 2 = >10% to 50% and score 3 = >50%. If the staining in tumor cells was ≥10% (scores 2 and 3), it was considered positive. The patients with L1CAM positivity had significantly more frequent lymphovascular space invasion and lymph node metastasis than patients with L1CAM negativity (P = 0.013 and P = 0.007). L1CAM expression was strongly associated with mutant p53 (P = 0.003). Recurrence was significantly higher (P = 0.001) and overall survival and progression-free survival were significantly lower in patients with L1CAM positivity (P = 0.001 for both). Seventy-nine patients (52.7%) were put into NSMP group. About 84.8% of them (n = 67) were L1CAM negative and 15.2% of them (n = 12) were L1CAM-positive. Recurrence was significantly higher (P = 0.001) and overall survival and progression-free survival were significantly lower in patients with NSMP who were positive for L1CAM (P = 0.002 and P = 0.001, respectively). This study demonstrates that L1CAM expression status may add prognostic information to endometrial cancer, particularly in the NSMP subgroup. Considering the prognostic importance of L1CAM, its use as a marker may make significant contributions to reducing prognostic heterogeneity, especially in the NSMP subgroup.

Frequency of lymph node metastases at different neck levels in patients with oral squamous cell carcinoma: a systematic review and meta-analysis.

Currently, neck dissection is a standard treatment for the majority of oral squamous cell carcinoma (OSCC) patients. However, the procedure can lead to a series of complications, significantly reducing patient quality of life and even affecting the antitumor immune response in patients undergoing immunotherapy. Therefore, in the era of precision surgery, gaining a deeper understanding of the patterns of lymph node metastasis (LNM) in OSCC is crucial. Literature searches were performed on PubMed, Embase, Web of Science, Cochrane Library, WANFANGDATA and China National Knowledge Infrastructure (CNKI) (inception to April 10, 2024). In addition, a manual searching was conducted in Scopus, Google Scholar, and Education Resources Information Center (ERIC). We included observational studies that evaluated the frequency of LNM in OSCC patients. Systematic review and a random effects model meta-analysis were performed. The search identified 4694 articles, of which 17 studies included in our study. We calculated the frequency of LNM according to the data reported in the articles. Frequency of LNM=number of patients with positive lymph node / number of patients with OSCC. The frequency of LNM was 12% in level I (95%CI: 0.11 to 0.15, I2=38.01%), 20% in level II (95%CI: 0.17 to 0.22, I2=47.71%), 10% in level III (95%CI: 0.08 to 0.12, I2=49.10%), 2% in level VI (95%CI: 0.01 to 0.03, I2=27.58%), 1% in level V (95%CI: 0.00 to 0.01, I2=11.37%). The frequency of LNM is consistent with the "cascade theory" and appears to be no significant difference from different primary sites. The frequency of LNM were low in levels I-III and were very low in level IV-V which implicated that more conservative treatments may be considered for OSCC in the future. This study will help clinicians better determine the extent of surgery and preserve lymph nodes during neck dissection.

Defining angioinvasion and lymphatic invasion in papillary thyroid carcinoma: morphological criteria, utility of D2-40/CD31/ERG immunohistochemistry and correlation with clinicopathological characteristics.

While CAP and ICCR protocols mandate the separation of angioinvasion (AI) and lymphatic invasion (LI) in thyroid carcinoma, distinction between them can be difficult. Because the presence of AI is used to stratify patients with papillary thyroid carcinoma (PTC), there is a need to accurately diagnose AI and LI. AI and LI were evaluated in 162 cases of PTC (n = 155) and high-grade differentiated thyroid carcinoma, papillary phenotype (HGDTCp, n = seven) using haematoxylin and eosin (H&E), D2-40 and CD31/ERG. In encapsulated carcinomas, vascular invasion (VI) was only of AI nature. Infiltrative carcinomas showed LI (46 of 131, 35%) and AI (19 of 131, 16%). The frequency of nodal metastasis (NM) and large volume of NM was 93 and 85%, respectively, in tumours with LI, and 39 and 26%, respectively, in those without LI. Luminal red blood cells and smooth muscle in the wall of large-calibre vessels were not reliable criteria to exclude LI and were seen in 23 and 6% of LI, respectively. LI was an independent predictor for NM, whereas AI is an independent predictor for distant metastasis at presentation in PTC/HGDTCp. VI in encapsulated carcinomas, including follicular variant PTC, is only of AI nature, confirming the position of this variant as a close entity to follicular carcinoma rather than classic PTC, whereas infiltrative PTC/HGDTCp may have LI or, less frequently, AI. As no morphological features reliably distinguish LI from AI, D2-40 and CD31/ERG immunostains should be considered for separating AI from LI when dealing with vascular invasion in an infiltrative PTC.

A case of early-stage type 3 gastric neuroendocrine tumor in the upper body of the stomach: is endoscopic resection feasible?

Although gastric neuroendocrine tumors (NETs) are uncommon compared with gastric carcinomas, the incidence of NETs has been recently increasing. Gastric NETs are classified into three subgroups, and among these, gastrin-independent sporadic type 3 gastric NETs have a poor prognosis because of frequent lymph node or distant metastasis. We experienced a case of an early-stage type 3 gastric NET associated with lymphovascular and submucosal invasion. In a 54year-old woman, esophagogastroduodenoscopy performed during a health screening identified an elevated lesion of the upper body of the stomach. The results of immunohistochemical analyses of endoscopic biopsy specimens obtained from the lesion were positive for chromogranin A and synaptophysin, indicating an NET. Because the patient's serum gastrin level was normal and she had no predisposing conditions for NET development, the tumor was diagnosed as a type 3 gastric NET. The patient underwent local resection of the tumor and regional lymph node dissection. The resected specimen indicated a diagnosis of type 3 gastric NET with invasion into the submucosa and lymphatic duct. This is an extremely rare case of an early-stage type 3 gastric NET. Our discussion provides insight into the pathogenesis and development of these tumors and the appropriate therapeutic strategy.

Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related mortality worldwide. Mesenchymal-epithelial transition factor (MET) gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor treatment. MET amplification has been reported in CRC, but data are very limited. Investigating pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical practice. To determine the pathological significance of MET amplification in CRC and to propose a feasible screening strategy. A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen Cancer Hospital of Chinese Academy of Medical Sciences were recruited. All patients were without RAS/RAF mutation or microsatellite instability-high. MET amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Correlations between MET aberration and pathological features were detected using the chi-squared test. Progression free survival (PFS) during the two-year follow-up was detected using the Kaplan-Meier method and log rank test. The results of MET FISH and IHC were compared using one-way ANOVA. Polysomy-induced MET amplification was observed in 14.4% of cases, and focal MET amplification was not detected. Polysomy-induced MET amplification was associated with a higher frequency of lymph node metastasis (LNM) (P < 0.001) and higher tumor budding grade (P = 0.02). In the survival analysis, significant difference was detected between patients with amplified- and non-amplified MET in a two-year follow-up after the first diagnosis (P = 0.001). C-MET scores of 0, 1+, 2+, and 3+ were observed in 1.4%, 24.9%, 54.7%, and 19.0% of tumors, respectively. C-MET overexpression correlated with higher frequency of LNM (P = 0.002), but no significant difference of PFS was detected between patients with different protein levels. In terms of concordance between MET FISH and IHC results, MET copy number showed no difference in c-MET IHC 0/1+ (3.35 ± 0.18), 2+ (3.29 ± 0.11) and 3+ (3.58 ± 0.22) cohorts, and the MET-to-CEP7 ratio showed no difference in three groups (1.09 ± 0.02, 1.10 ± 0.01, and 1.09 ± 0.03). In CRC, focal MET amplification was a rare event. Polysomy-induced MET amplification correlated with adverse pathological characteristics and poor prognosis. IHC was a poor screening tool for MET amplification.

Early gastric cancer with RhoGAP fusion is linked to frequent nodal metastasis and a part of microtubular-mucocellular histology.

Gastric cancer with fusion genes involving the Rho GTPase-activating protein domain (RhoGAP-GC) is mainly included in the genomically stable type of The Cancer Genome Atlas classification. Clinical implications and histological characteristics of RhoGAP-GC in the early phase remain unclear. We analyzed 878 consecutive pT1b GCs for RhoGAP and its partner genes using fluorescence in situ hybridization assay. RhoGAP fusion was detected in 57 (6.5%) GCs. Univariate analysis revealed that female sex, middle-lower third tumor location, advanced macroscopic type, tumor diameter > 2cm, pT1b2, lymphatic invasion, venous invasion, negative EBER-ISH, and RhoGAP fusion were significantly associated with lymph node metastasis (LNM). Multivariate analysis presented RhoGAP fusion, lymphatic invasion, tumor diameter > 2cm, advanced macroscopic type, venous invasion, and middle-lower third tumor location as independent risk factors for LNM. Notably, RhoGAP fusion had the highest odds ratio (3.92) for LNM among analyzed parameters (95% CI 2.12-7.27; p < 0.001). Compared to non-RhoGAP-GCs, RhoGAP-GCs were significantly frequent in younger females and showed the highest incidence of lymphatic invasion (56.2%) and LNM (49.1%) (p < 0.001). Histologically, microtubular architecture with pseudo-trabecular interconnection and small aggregations of tumor cells with a varied amount of cytoplasmic mucin, named "microtubular-mucocellular (MTMC) histology," was found in 93.0% (53 of 57) of RhoGAP-GCs in the intramucosal area. MTMC histology showed high sensitivity and negative predictive value (93.0% and 99.4%, respectively) for RhoGAP fusion, albeit positive predictive value is low (34.9%). RhoGAP-GC is linked to a characteristic MTMC histology and a high incidence of LNM.

Risk factors and prognosis for supraclavicular lymph node metastasis in patients with thoracic esophageal cancer. Distant or regional metastasis?

We aimed to determine the frequency and prognosis of supraclavicular (#104) lymph node (LN) metastasis compared with other LN stations in patients with advanced thoracic esophageal cancer and to identify risk factors for metastasis to delineate the indications for three-field lymphadenectomy (3FL). The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography-positive LNs. The efficacy index (EI), calculated from the frequency of LN metastases and survival rates, was used as prognostic value of each LN station dissection for patient survival. Risk factors for #104 LN metastasis were determined by multivariable logistic regression. The frequency of #104 LN metastasis was 11.6% overall, 31.7% in upper and 8.3% in middle/lower third lesion. Neoadjuvant chemotherapy was administered to 71% of patients and chemo-radiation to 11%. The 5-year overall survival was 45.8%. The EI for #104 LNs (5.3) was similar to that for #101 LNs. Risk factors were age < 65years, upper third lesion, clinical N2-3, #101/106rec LN metastasis and poorly differentiated carcinoma. The 5-year overall survival of patients with middle/lower lesions was 38% (EI 3.1), similar to that for #101 and #8/9/11 LNs. The prognosis of patients with #104 LN metastases is similar to that of patients with metastases in other regional LN stations. Therefore, we recommend 3FL exclusively for patients at a high risk of #104 LN metastasis due to the overall metastatic rate not being high.

Surgical interpretation of the WHO subclassification of intrahepatic cholangiocarcinoma: a narrative review.

Intrahepatic cholangiocarcinoma (iCCA) has been subclassified by its gross morphology into the mass-forming (MF), periductal-infiltrating (PI), and intraductal growth (IG) types and their combinations. This classification correlates well with clinical features; for example, MF-iCCA has less lymph-node metastasis and a better prognosis than PI-iCCA. According to the recently accumulated evidence from histological investigations, the WHO classification endorsed a subclassification scheme in which iCCA cases are classified into small- and large-duct types. Small-duct iCCA is considered to originate from septal or smaller bile ducts and is characterized by less frequent lymph-node metastasis, a favorable prognosis, and an MF appearance. Large-duct iCCA arises around the second branch of the biliary tree and has more aggressive biology and distinct genetic abnormalities. According to the practice guidelines for iCCA from the Liver Cancer Study Group of Japan and the National Comprehensive Cancer Network, upfront surgery is recommended for iCCA without distant metastasis regardless of the morphological subtype, based on clinical experience. In consideration of the biological heterogeneity of iCCA, the treatment strategy for iCCA needs to be reconsidered based on the WHO subtypes.

Metachronous remnant gastric cancer after proximal gastrectomy.

260 Background: Proximal gastrectomy is frequently selected for early gastric cancer located at the upper third of the stomach. Annual postoperative endoscopy is considered to be useful for the early detection of metachronous remnant gastric cancer (MRGC). Despite that, we sometimes have also encountered cases that are not suitable for endoscopic resection (ER). The aim of this study is to identify the risk factors for the patients who developed MRGC after proximal gastrectomy, received annual endoscopy, but are not eligible for ER (non-ER). Methods: We retrospectively analyzed 191 patients who had received annual endoscopic surveillance after undergoing PG for cT1 gastric cancer at NCCH between 2006-2015. MRGCs were categorized into two groups: ER group and non-ER group. The remnant stomach was defined as three locations: pseudo-fornix (PF), corpus and antrum. Results: The median observation period was 73 (range 12-168) months. MRGC was observed in 29 cases with 32 lesions. ER was eligible for 20 lesions (ER group, 62.5%), but 12 were not (non-ER group, 37.5%). We compared the characteristics between of ER group and non-ER group in terms of sex, age (&gt;65 years), interval from the initial surgery (&gt;60months), the location (PF vs non-PF), and cross-sectional circumference (posterior wall vs. others). In both univariate and multivariate logistic regression analysis, only the location at PF was identified as a risk factor for non-ER group (OR 25.0, 95% CI: 1.8–339, p = 0.015). Among 12 lesions of the non-ER group, the location of PF was found in 6 (50%) lesions. As compared with MRGC at the non-PF, that at the PF (n = 6) was characterized by younger patients (57.5 (range 37-69) years vs. 69 (56-77) years), larger size (36 (7-57) mm vs. 9 (9-24) mm), deeper depth (MP or deeper; 5/6 vs. 0/6), more frequent undifferentiated-type histology (4/6 vs. 0/6) and frequent nodal metastasis (3/6 vs. 0/6). The interval to detect MRGC appears to be longer in the PF (78 (31-96) months than that of the non-PF (60 (31-96) months), but the difference was not statistically significant (p = 0.86). Then, we examined the visibility and the mucosal normality of the area developing MRGC in the annual follow-up endoscopy one year before the detection of MRGC (n =32). In 25 lesions at the non-PF, the visibility and the mucosal normality was secured in 21 (84%). while 5 PF lesions were difficult to observe (71.4%, p = 0.01) due to food residues in 4 (57%, p = 0.047) and insufficient expansion of the gastric mucosa in 4 (57%, p = 0.001). Conclusions: Detection of the MRGC at the PF at an early stage is crucial and challenging. With annual follow-up endoscopy, complete clearance and adequately extending the gastric mucosa could lead to the early detection of MRGC at the PF.

Prognostic significance of lymph node metastasis in pancreatic tail cancer: A multicenter retrospective study.

Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt-PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt-PDAC. This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt-PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt-PDAC prognosis were investigated. There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt-PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence-free survival (HR = 2.01, 95% CI = 1.33-3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence-free survival. LN dissection along the hepatic artery for Pt-PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short-term outcomes and preservation of pancreatic function is required.

Comparing Characteristics of Pelvic High-grade Serous Carcinomas with and without Breast Cancer Gene Variants on MR Imaging.

To compare MRI findings of high-grade serous carcinoma (HGSC) with and without breast cancer (BRCA) gene variants to explore the feasibility of MRI as a genetic predictor. We retrospectively reviewed MRI data from 16 patients with BRCA variant-positive (11 patients of BRCA1 and 5 patients of BRCA2 variant-positive) and 32 patients with BRCA variant-negative HGSCs and evaluated tumor size, appearance, nature of solid components, apparent diffusion coefficient (ADC) value, time-intensity curve, several dynamic contrast-enhanced curve descriptors, and nature of peritoneal metastasis. Age, primary site, tumor stage, bilaterality, presence of lymph node metastasis, presence of peritoneal metastasis, and tumor markers were also compared between the groups with the Mann-Whitney U and chi-square tests. The mean tumor size of BRCA variant-positive HGSCs was 9.6 cm, and that of variant-negative HGSCs was 6.8 cm, with no significant difference (P = 0.241). No significant difference was found between BRCA variant-positive and negative HGSCs in other evaluated factors, except for age (mean age, 53 years old; range, 32-78 years old for BRCA variant-positive and mean age, 61 years old; range, 44-80 years old for BRCA variant-negative, P = 0.033). Comparing BRCA1 variant-positive and BRCA2 variant-positive HGSCs, BRCA1 variant-positive HGSCs were larger (P = 0.040), had greater Max enhancement (P = 0.013), Area under the curve (P = 0.013), and CA125 (P = 0.038), and had a higher frequency of lymph node metastasis (P = 0.049), with significance. There was no significant difference in the MRI findings between patients with HGSCs with and without BRCA variants. Although studied in small numbers, BRCA1 variant-positive HGSCs were larger and more enhanced than BRCA2 variant-positive HGSCs with higher CA125 and more frequent lymph node metastases, and may represent more aggressive features.

Breast Carcinoma: Correlation of Molecular Subtypes with Histopathologic Characteristics

Context: Breast carcinoma is a heterogenous disease and similar histological subtypes may exhibit different behavior and treatment response. The molecular classification may provide better prognostic, predictive and therapeutic information than histological classification. The study aimed at evaluating the distribution of molecular subtypes of breast cancer and its association with prognostic factors. Method: This prospective cross-sectional study was conducted on breast cancer cases, over a period of 2 years, at M.S. Ramaiah Medical College and Hospitals, Bengaluru. The resection specimens were evaluated for histopathological features. Immunohistochemical analysis for ER, PR, Her2neu and Ki-67 expression was performed to identify molecular subtypes. Correlation of molecular subtypes with histopathological prognostic factors was done by Chi- square test or Fischer’s exact test. Results: A total of 85 cases were evaluated and classified into Luminal A (50.6%), Basal like (27%), Luminal B (11.8%) and HER-2 enriched (10.6%) molecular subtypes. Invasive ductal carcinoma was the commonest histologic type across all the molecular subtypes. Majority of low-grade tumors were Luminal A and most of high-grade tumors were Basal like (p= 0.004). HER-2 enriched and Basal like tumors were relatively more frequent in ≤ 50 years of age and Luminal A tumors exhibited less frequent lymph node metastasis. However, these associations fell short of statistical significance. Conclusion: Luminal A tumors are the most common molecular subtype. Statistically significant correlation exists between histologic grade and molecular subtype. There is no significant correlation between molecular subtype and age, tumor size, nodal metastasis, pathological T stage and TNM stage. Keywords: Basal like, Breast carcinoma, HER2­Enriched, Luminal A, Luminal­ B, Molecular subtypes

Retraction: Kinesin family member 2A serves as a potential biomarker reflecting more frequent lymph node metastasis and tumor recurrence risk in basal-like breast cancer patients.

[This retracts the article DOI: 10.3389/fsurg.2022.889294.].

Inflammatory cytokine-regulated LNCPTCTS suppresses thyroid cancer progression via enhancing Snail nuclear export

Lymph node metastases are commonly observed in diverse malignancies where they promote cancer progression and poor outcomes, although the molecular basis is incompletely understood. Thyroid cancer is the most prevalent endocrine neoplasm characterized by high frequency of lymph node metastases. Here, we uncover an inflammatory cytokines-controlled epigenetic program during thyroid cancer progression. LNCPTCTS acts as a novel tumor suppressive lncRNA with remarkably decreased expression in thyroid cancer specimens, especially in metastatic lymph nodes. Inflammatory cytokines TNFα or CXCL10, which are released from tumor microenvironment (TME), impair binding capabilities of the transcription factor (TF) EGR1 to the LNCPTCTS promoter and reduce the lncRNA expression in cells. Notably, LNCPTCTS binds to eEF1A2 protein and facilitates the interaction between eEF1A2 and Snail, which promotes Snail nucleus export via the RanGTP-Exp5-aa-tRNA-eEF1A2 complex. Loss of LNCPTCTS in tumors leads to accumulation of Snail in the nucleus, suppressed transcription of E-cadherin and PEBP1, reduced E-cadherin and PEBP1 protein levels, and activated epithelial-mesenchymal transition and MAPK signaling. Our results reveal what we believe to be a novel paradigm between TME and epigenetic reprogram in cancer cells which drives lymph node metastases, therefore illuminating the suitability of LNCPTCTS as a targetable vulnerability in thyroid cancer.

Tumor Budding Should Be in Oral Cavity Cancer Reporting: A Retrospective Cohort Study Based on Tumor Microenvironment.

The utility of histological grading, which is useful in predicting prognosis in many tumors, is controversial for oral squamous cell carcinoma (OSCC). Therefore, new histopathological parameters should be added to histopathology reports of OSCCs. The study aimed to evaluate the parameters of worst invasion pattern (WPOI) and tumor budding in patients with OSCC, to compare them with other histopathological parameters, clinical data and overall survival, and to evaluate these results within the literature. A total of 73 OSCC cases with excisional biopsies were included in this study. WPOI, tumor budding, cell nest size, tumor-stroma ratio, stromal lymphocyte infiltration and stroma type, as well as classical histopathological parameters, were evaluated on hematoxylin-eosin-stained sections. Perineural invasion, lymph node metastases, advanced stage, presence of more than five buds and single cell invasion pattern in univariate survival analyses are characterized by a shortened overall survival time. While there was no significant difference between WPOI results and survival in the survival analysis, WPOI 5 was associated with more frequent lymph node metastasis and advanced stage at the time of diagnosis compared to WPOI 4. We concluded that tumor budding and single-cell invasion should be considered prognostic histopathologic parameters in OSCC.

Routine elastin staining improves venous invasion detection in colorectal carcinoma

BackgroundColorectal carcinoma is the second most common cause of cancer-related deaths in North America. Invasion of tumor cells into lymphatic and blood vessels is an imperative step in the metastatic progression of colorectal carcinoma. ObjectivesThis is a before-and-after study conducted by the Department of Pathology and Laboratory Medicine of Mount Sinai Medical Center of Florida to assess the impact on venous invasion (VI) detection by implementing routine elastin staining on all tumor-containing blocks per case, where feasible, in colorectal carcinoma (CRC) resection specimens. MethodsClinicopathological parameters of CRC specimens were collected from January until December 2021 (n = 93) for the pre-implementation cohort and from January until December 2022 (n = 61) for the post-implementation cohort. ResultsVI detection was significantly increased in the post-implementation cohort at a rate of 50.8 % compared to only 18.6 % in the pre-implementation cohort. The majority of VI identified in the pre-implementation cohort was extramural (61.5 %), whereas in the post-implementation cohort it was intramural (41.9 %). On univariate analysis, implementation of routine elastin stain was associated with strikingly increased VI detection rates (OR = 4.5, p-value < 0.001). On multivariate analysis, after adjusting for other clinicopathologic variables, elastin staining retained its independent statistically significant impact on VI detection (OR = 2.6, p-value = 0.034). Of note, there were no significant differences in the pre- and post-implementation cohorts in the frequency of nodal metastases, tumor extent, histologic grade, perineural invasion, T stage or M stage. ConclusionBased on our results and what has been published recently, we confirm an increase in the VI detection rate after implementing routine elastin staining on all tumor-containing blocks in CRC resection specimens.

Immune-Related Long Non-Coding RNA Signatures for Tongue Squamous Cell Carcinoma

Tongue squamous cell carcinoma (TSCC) represents one of the major subsets of head and neck cancer, which is characterized by unfavorable prognosis, frequent lymph node metastasis, and high mortality rate. The molecular events regulating tongue tumorigenesis remain elusive. In this study, we aimed to identify and evaluate immune-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in TSCC. The lncRNA expression data for TSCC were obtained from The Cancer Genome Atlas (TCGA) and the immune-related genes were downloaded from the Immunology Database and Analysis Portal (ImmPort). Pearson correlation analysis was performed to identify immune-related lncRNAs. The TCGA TSCC patient cohort was randomly divided into training and testing cohorts. In the training cohort, univariate and multivariate Cox regression analyses were used to determining key immune-related lncRNAs, which were then validated through Cox regression analysis, principal component analysis (PCA), and receiver operating characteristic (ROC) analysis in the testing cohort. Six immune-related signature lncRNAs (MIR4713HG, AC104088.1, LINC00534, NAALADL2-AS2, AC083967.1, FNDC1-IT1) were found to have prognostic value in TSCC. Multivariate and univariate cox regression analyses showed that the risk score based on our six-lncRNA model, when compared to other clinicopathological factors (age, gender, stage, N, T), was an important indicator of survival rate. In addition, Kaplan-Meier survival analysis demonstrated significantly higher overall survival in the low-risk patient group than the high-risk patient group within both training and testing cohorts. The ROC analysis indicated that the AUCs for 5-year overall survival were 0.790, 0.691, and 0.721, respectively, for training, testing, and entire cohorts. Finally, PCA analysis demonstrated that the high-risk and low-risk patient groups presented significant deviation regarding their immune status. A prognostic model based on six immune-related signature lncRNAs was established. This six-lncRNA prognostic model has clinical significance and may be helpful in the development of personalized immunotherapy strategies.

The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer-Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy.

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive and heterogeneous groups of human neoplasms. HNSCC is characterized by high morbidity, accounting for 3% of all cancers, and high mortality with ~1.5% of all cancer deaths. It was the most common cancer worldwide in 2020, according to the latest GLOBOCAN data, representing the seventh most prevalent human malignancy. Despite great advances in surgical techniques and the application of modern combinations and cytotoxic therapies, HNSCC remains a leading cause of death worldwide with a low overall survival rate not exceeding 40-60% of the patient population. The most common causes of death in patients are its frequent nodal metastases and local neoplastic recurrences, as well as the relatively low response to treatment and severe drug resistance. Much evidence suggests that the tumour microenvironment (TME), tumour infiltrating lymphocytes (TILs) and circulating various subpopulations of immunocompetent cells, such regulatory T cells (CD4+CD25+Foxp3+Tregs), cytotoxic CD3+CD8+ T cells (CTLs) and CD3+CD4+ T helper type 1/2/9/17 (Th1/Th2/Th9/Th17) lymphocytes, T follicular helper cells (Tfh) and CD56dim/CD16bright activated natural killer cells (NK), carcinoma-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (N1/N2 TANs), as well as tumour-associated macrophages (M1/M2 phenotype TAMs) can affect initiation, progression and spread of HNSCC and determine the response to immunotherapy. Rapid advances in the field of immuno-oncology and the constantly growing knowledge of the immunosuppressive mechanisms and effects of tumour cancer have allowed for the use of effective and personalized immunotherapy as a first-line therapeutic procedure or an essential component of a combination therapy for primary, relapsed and metastatic HNSCC. This review presents the latest reports and molecular studies regarding the anti-tumour role of selected subpopulations of immunocompetent cells in the pathogenesis of HNSCC, including HPV+ve (HPV+) and HPV-ve (HPV-) tumours. The article focuses on the crucial regulatory mechanisms of pro- and anti-tumour activity, key genetic or epigenetic changes that favour tumour immune escape, and the strategies that the tumour employs to avoid recognition by immunocompetent cells, as well as resistance mechanisms to T and NK cell-based immunotherapy in HNSCC. The present review also provides an overview of the pre- and clinical early trials (I/II phase) and phase-III clinical trials published in this arena, which highlight the unprecedented effectiveness and limitations of immunotherapy in HNSCC, and the emerging issues facing the field of HNSCC immuno-oncology.