The role of tumour-associated tissue eosinophilia as a prognostic indicator in head and neck squamous cell carcinoma

Background Eosinophils are bone marrow-derived granulocytes known to have an imperative role in tissue inflammation. The mechanism of tumour-associated tissue eosinophilia (TATE) in head and neck cancers is however not well understood, and its role as a prognosticator is under evaluation. The aim of this study was to evaluate the association of TATE with factors associated with head and neck cancer and to assess its role as a prognostic marker in such patients. Results 102 males and 24 females comprised the study population, and 34.9% of which were in the age group of 41 to 50 years. Amongst these 126 patients, most (37.3%) presented in stage III followed by stage IV (28.6%). 29.4% had well-differentiated SCC, 55.6% had moderately differentiated SCC, and 15% were diagnosed with poorly differentiated SCC. 42.8% had TATE grade II, followed by grade III (29.4%) and grade I (27.8%). Correlation studies showed that factors significantly associated with TATE were age, site and tumour differentiation. While 45.7% poorly differentiated tumours showed grade I eosinophilia, 51.4% of well-differentiated tumours had grade III TATE. Conclusions TATE showed a highly significant association with tumour differentiation, suggestive of eosinophils partaking a tumouricidal role. This association may be utilised as a convenient early prognosticator for head and neck cancers and should be made a regular feature of biopsy reports. Furthermore, it may be utilised in planning and adopting appropriate treatment modalities in malignancies predicted to have an aggressive course.

CD44 and E-Cadherin Expression in Primary Epithelial Tumours of Ovary and Comparison with Histological Type and Tumour Differentiation - A Cross-Sectional Study from Thrissur, Kerala

BACKGROUND Ovarian tumours are the common cause of morbidity and mortality in women worldwide. Primary epithelial ovarian tumours comprise the majority. Cluster differentiation 44 (CD-44) is a trans-membrane glycoprotein which plays a role in cell- cell interaction, adhesion and migration, leading to the progression and metastasis of tumour. E-cadherin is another cell adhesion molecule which plays an important role in neoplastic progression. So, it is necessary to find out the relationship of CD-44 and E-cadherin expression with histological types and tumour differentiation, which might predict the prognosis. The present study was undertaken to assess the pattern of expression of CD-44 and E-cadherin in primary epithelial tumours of ovary and to determine the relationship between their expression with age, histological type and tumour differentiation. METHODS This is a cross-sectional study conducted in the Department of Pathology, Government Medical College, Thrissur; a tertiary care institution. Histological types and tumour differentiation for each case was determined from haematoxylin and eosin sections. Immunohistochemical stain for CD-44 and E-cadherin was done. Pattern of expression was studied and a semi quantitative score was calculated. Expression of both markers was then compared with the age, histological type and tumour differentiation. RESULTS Out of 57 cases studied, majority of the patients had serous (21 cases) or mucinous tumours (20 cases). The mean age group was 54.5 years. CD-44 expression was significantly correlated with tumour differentiation but there was no correlation found with age and histological type. In E-cadherin expression, there was no correlation with age, histological type and tumour differentiation. CONCLUSIONS For primary epithelial tumours, expression of CD-44 could be an indicator for tumour progression, invasiveness or distant metastasis. Poorly differentiated tumours with increased expression may be helpful in predicting disease progression. Target therapy can be employed in such cases. In case of E-cadherin which is said to be a prognostic marker, more studies help in bridging the gap between prognosis and outcome. KEYWORDS CD-44, E-cadherin, Immunohistochemistry, Epithelial Ovarian Tumours f

Expression of programmed death-ligand 1 protein in pulmonary squamous cell carcinoma correlates with tumour necrosis but not with tumour differentiation

AimsPulmonary squamous cell carcinoma (SqCC) represents the second most common non-small cell lung carcinoma type. The mechanisms which regulate programmed death ligand 1 (PD-L1) expression in this form of lung cancer are not fully elucidated yet.MethodsWe immunohistochemically determined the level of PD-L1 expression using the Tumour Proportion Score system in surgical resections of 133 patients with pulmonary SqCC. The results from PD-L1 immunohistochemistry were analysed in relation to tumour differentiation and the presence of necrotic areas comprising at least 20% of the tumour mass.ResultsNo significant differences in terms of PD-L1 expression were found between SqCC subtypes as defined by the current WHO classification: better differentiated, keratinising tumours (12/24, 50.0 %) compared with less differentiated, non-keratinising and basaloid forms (62/109, 56.9 %) were PD-L1 positive in a comparable proportion of cases (p=0.1903). Contrary to that, SqCCs with the presence of necrosis (51/61, 83.6 %) had significantly more PD-L1-positive cases (p<0.001) compared with SqCCs without necrotic areas (23/72, 32.0 %)ConclusionsWe demonstrated that PD-L1 expression in pulmonary SqCCs does not correlate with the traditionally defined degree of differentiation of these tumours. On the other hand, we found a significant association between the positive result of PD-L1 immunohistochemistry and tumour necrosis. Further investigation regarding the role of hypoxic pathways as presumable inducers of PD-L1 expression in pulmonary SqCCs might contribute to the understanding of this phenomenon.

Analysis of transcriptome in the relationship between expression of PRC1 protein and prognosis of patients with cholangiocarcinoma

Objective To investigate whether protein regulator of cytokinesis 1 ( PRC1), which is involved in the regulation of human carcinogenesis, contributes to poor prognosis in patients with cholangiocarcinoma (CCA). Methods Data and tissues from patients with CCA were retrospectively studied. Immunohistochemical staining and western blotting were used to evaluate and contrast the PRC1 expression profile at the protein level in CCA tumour and pericarcinomatous tissues from the same study population. Relationships between clinical characteristics and patient survival were observed using univariate and multivariate analyses. Correlations between PRC1 expression and clinical characteristics were analysed by logistic regression. Results A total of 45 patients were included. PRC1 expression was found to be upregulated in CCA cancer tissues versus pericarcinomatous tissues. Overexpression of PRC1 was shown to be related to tumour differentiation, tumour node metastasis staging and lymph node metastasis, and was also revealed to be an independent marker of poor CCA prognosis. Conclusions The present results suggest that PRC1 may be a prognostic and therapeutic biomarker for patients with CCA.

Predicting postoperative peritoneal metastasis in gastric cancer with serosal invasion using a collagen nomogram

Accurate prediction of peritoneal metastasis for gastric cancer (GC) with serosal invasion is crucial in clinic. The presence of collagen in the tumour microenvironment affects the metastasis of cancer cells. Herein, we propose a collagen signature, which is composed of multiple collagen features in the tumour microenvironment of the serosa derived from multiphoton imaging, to describe the extent of collagen alterations. We find that a high collagen signature is significantly associated with a high risk of peritoneal metastasis (P < 0.001). A competing-risk nomogram including the collagen signature, tumour size, tumour differentiation status and lymph node metastasis is constructed. The nomogram demonstrates satisfactory discrimination and calibration. Thus, the collagen signature in the tumour microenvironment of the gastric serosa is associated with peritoneal metastasis in GC with serosal invasion, and the nomogram can be conveniently used to individually predict the risk of peritoneal metastasis in GC with serosal invasion after radical surgery.

Mathematical Models for Intraoperative Prediction of Metastasis to Lymph Nodes in the Hilar-intrapulmonary or the Mediastinal Region in Patients With Clinical Stage I Non-small Cell Lung Cancer: a Retrospective Cohort Study

Background: It remains challenging to determine the regions of metastasis to lymph nodes during operation for clinical stage I non-small cell lung cancer (NSCLC). This study aimed to establish intraoperative mathematical models with nomograms for predicting the hilar-intrapulmonary node metastasis (HNM) and the mediastinal node metastasis (MNM) in patients with clinical stage I NSCLC.Methods: The clinicopathological variables of 585 patients in a derivation cohort who underwent thoracoscopic lobectomy with complete lymph node dissection were retrospectively analysed for their association with the HNM or the MNM. After analysing the variables, we developed multivariable logistic models with nomograms to estimate the risk of lymph node metastasis in different regions. The predictive efficacy was then validated in a validation cohort of 418 patients.Results: It was confirmed that CEA (> 5.75 ng/ml), CYFRA211 (> 2.85 ng/ml), the maximum diameter of tumour (> 2.75 cm), tumour differentiation (grade III), bronchial mucosa and cartilage invasion, and vascular invasion were predictors of HNM, and CEA (>8.25 ng/ml), CYFRA211 (> 2.95 ng/ml), the maximum diameter of tumour (> 2.75 cm), tumour differentiation (grade III), bronchial mucosa and cartilage invasion, vascular invasion, and visceral pleural invasion were predictors of MNM. The validation of the prediction models based on the above results demonstrated good discriminatory power.Conclusions: Our predictive models are helpful in the decision‑making process of specific therapeutic strategies for the regional lymph node metastasis in patients with clinical stage I NSCLC.

Application of integrated positron emission tomography/magnetic resonance imaging in evaluating the prognostic factors of head and neck squamous cell carcinoma with positron emission tomography, diffusion-weighted imaging, dynamic contrast enhancement and combined model

Objectives: This study was designed to investigate the distribution of the independent parameters of PET and MR in tumour differentiation and staging and to evaluate the diagnostic efficiency of the independent parameters and combined model of PET/MR in the tumour differentiation of head and neck squamous cell carcinoma (HNSCC). Methods: The patients with the preliminary diagnosis of HNSCC were included and underwent the integrated PET/MR The parameters included the diffusion-weighted imaging, dynamic contrast enhancement and PET. The correlations between different parameters and the distribution in groups of tumour differentiation and staging were analysed. The combined model was established with complementary PET/MR parameters. The diagnostic efficiency of the independent parameters and combined model in the tumour differentiation were analysed by receiver operating characteristic curve. Results: The correlations between the parameters of dynamic contrast enhancement and PET were most significant. There were significant differences between the well-differentiated group and the moderately/poorly differentiated group in terms of the mean values of apparent diffusion coefficient (ADC) and standardised uptake value (SUV) (p < 0.05). The distributions among different tumour stage groups were not statistically different in all the parameters. The diagnostic efficiency of tumour differentiation increased in the order of Kepmean, SUVmean, ADCmean, and the combined model. Conclusions: Compared with the independent parameter, the combination of multiple parameters with PET/MR can further improve the diagnostic performance of tumour differentiation in HNSCC.

IKKα as a potential novel target for treatment of colorectal cancer.

174 Background: Colorectal cancer (CRC) is a heterogeneous disease leading to different survival outcomes for patients with the same stage of disease. The non-canonical NF-κB pathway has been shown to have a key role in tumorigenesis, and the aim of this study was to investigate the role of IKKα, the main catalytic component of this pathway in CRC. Methods: A tissue microarray was retrospectively constructed from a patient cohort (1033) with stage I-III CRC who underwent surgery. IHC was utilised to examine cytoplasmic and punctate IKKα expression and determine any association with clincopathological features and cancer specific survival (CSS). To assess IKKα inhibition, organoids were prepared from wild type (WT) mouse colon, mouse models of CRC (Apc and Apc.KRAS.pT53.TGFbR2 (AKPT)) and patient derived human organoids. These were treated with an IKKα inhibitor, SU1433 and organoid size and cell viability assessed. Results: High cytoplasmic expression of IKKα was associated with increasing T stage (p = 0.012), poor tumour differentiation (p = 0.010), tumour necrosis (p = 0.013) and low proliferation status (p = 0.013) but was not associated with CSS. High punctate IKKα expression associated with tumour differentiation (p = 0.001), necrosis (p = 0.004), proliferation (p = 0.044) and MMR competence (p < 0.001) and was also significantly associated with reduced CSS (HR1.20 95%CI 1.02-1.42, p < 0.001). SU1433 did not significantly impact on WT (C57/B16) organoid viability up to a concentration of 1 uM, however organoid size and cell viability was significantly reduced in a dose dependent manner in organoids from both Apc and AKPT mouse models. A similar reduction was observed in patient derived human organoids. Conclusions: Punctate IKKα expression was associated with poor cancer specific survival in CRC patients, and inhibition with SU1433, impacted on CRC mouse and patient derived human organoid size and cell viability. These results suggest that, following further investigation and confirmation, IKKα may be employed as a novel therapeutic target in CRC.