Maspin and Ezrina - Biomarker Molecules in Colorectal Cancer Correlative immunohistochemical study

The results of the recent years researches support the need for personalized therapeutic of cancer by completing the clinical, imagistic and histopathological diagnosis with molecular studies to identify new useful biomarkers for diagnosis, prognosis and tumor progression. Maspin is a non-inhibitory serine protease having a proapoptotic activity, suppressor of tumor invasion, metastasis and angiogenesis. Ezrin is a member of Ezrin/Radixin/Moesin (ERM) family, involved in cellular adhesion mechanisms, motility and invasiveness of tumor cells. In colorectal tumors, there is a heterogeneity of research results regarding the clinical significance of the maspin due to a possible partnership with other molecules with which it interacts through the same signaling pathways. Our study investigated the two molecule�s immunoreactivity (IR) in 92 colorectal tumors highlighting an inverse correlation between ezrin�s and maspin�s expression, suggesting the fact that ezrin�s overexpression could influence maspin�s tumoral suppressor role. Furthermore there was observed a difference of the molecules IR within the same tumoral stage, suggesting their utility regarding the treatment protocol of these tumors.

Download Full-text

Modulating Properties of Piroxicam, Meloxicam and Oxicam Analogues against Macrophage-Associated Chemokines in Colorectal Cancer

Molecules ◽

10.3390/molecules26237375 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7375

Author(s):

Paulina Lewandowska ◽

Izabela Szczuka ◽

Iwona Bednarz-Misa ◽

Berenika M. Szczęśniak-Sięga ◽

Katarzyna Neubauer ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Adenocarcinoma ◽

Normal Mucosa ◽

Colorectal Tumors ◽

Adjacent Tissue ◽

Inflammatory Drug ◽

Chemokine Expression ◽

Adenocarcinoma Cells ◽

Thiazine Ring ◽

N Stage

The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the expression/secretion of macrophage-associated chemokines (RTqPCR/Luminex xMAP) in colorectal adenocarcinoma cells, and on the expression of upstream the non-steroidal anti-inflammatory drug (NSAID)-activated genes NAG1, NFKBIA, MYD88, and RELA, as well as at the chemokine profiling in colorectal tumors. Meloxicam downregulated CCL4 9.9-fold, but otherwise the classic oxicams had a negligible/non-significant effect. Novel analogues with a thiazine ring substituted with arylpiperazine and benzoyl moieties significantly modulated chemokine expression to varying degree, upregulated NAG1 and NFKBIA, and downregulated MYD88. They inhibited CCL3 and CCL4, and their effect on CCL2 and CXCL2 depended on the dose and exposure. The propylene linker between thiazine and piperazine nitrogens and one arylpiperazine fluorine substituent characterized the most effective analogue. Only CCL19 and CXCL2 were not upregulated in tumors, nor was CXCL2 in tumor-adjacent tissue compared to normal mucosa. Compared to adjacent tissue, CCL4 and CXCL2 were upregulated, while CCL2, CCL8, and CCL19 were downregulated in tumors. Tumor CCL2 and CCL7 increased along with advancing T and CCL3, and CCL4 along with the N stage. The introduction of arylpiperazine and benzoyl moieties into the oxicam scaffold yields effective modulators of chemokine expression, which act by upregulating NAG1 and interfering with NF-κB signaling.

Download Full-text

A data-driven approach to a chemotherapy recommendation model based on deep learning for patients with colorectal cancer in Korea

10.21203/rs.2.21064/v4 ◽

2020 ◽

Author(s):

Jin-Hyeok Park ◽

Jeong-Heum Baek ◽

Sun Jin Sym ◽

KangYoon Lee ◽

Youngho Lee

Keyword(s):

Colorectal Cancer ◽

Deep Learning ◽

Decision Support ◽

Cancer Treatment ◽

Clinical Decision Support ◽

Treatment Guidelines ◽

Treatment Protocol ◽

Clinical Decision ◽

Actual Data ◽

Nccn Guidelines

Abstract Background: Clinical Decision Support Systems (CDSSs) have recently attracted attention as a method for minimizing medical errors. Existing CDSSs are limited in that they do not reflect actual data. To overcome this limitation, we propose a CDSS based on deep learning. Methods: We propose the Colorectal Cancer Chemotherapy Recommender (C3R), which is a deep learning-based chemotherapy recommendation model. Our model improves on existing CDSSs in which data-based decision making is not well supported. C3R is configured to study the clinical data collected at the Gachon Gil Medical Center and to recommend appropriate chemotherapy based on the data. To validate the model, we compared the treatment concordance rate with the National Comprehensive Cancer Network (NCCN) Guidelines, a representative set of cancer treatment guidelines, and with the results of the Gachon Gil Medical Center’s Colorectal Cancer Treatment Protocol (GCCTP). Results: For the CR3 model, the treatment concordance rates with the NCCN guidelines were 70.5% for Top-1 Accuracy and 84% for Top-2 Accuracy. The treatment concordance rates with the GCCTP were 57.9% for Top-1 Accuracy and 77.8% for Top-2 Accuracy. Conclusions: This model is significant, i.e., it is the first colon cancer treatment clinical decision support system in Korea that reflects actual data. In the future, if sufficient data can be secured through cooperation among multiple organizations, more reliable results can be obtained.

Download Full-text

CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood

International Journal of Molecular Sciences ◽

10.3390/ijms21165925 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5925

Author(s):

Daniëlle Krijgsman ◽

Natasja L. De Vries ◽

Morten N. Andersen ◽

Anni Skovbo ◽

Rob A.E.M. Tollenaar ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Outcome ◽

Disease Free Survival ◽

Soluble Form ◽

Clinicopathological Parameters ◽

Multiparameter Flow Cytometry ◽

Enzyme Linked Immunosorbent Assay ◽

Colorectal Tumors ◽

Blood Monocytes ◽

Tumor Associated Macrophages

The macrophage-associated molecule CD163 has been reported as a prognostic biomarker in different cancer types, but its role in colorectal cancer (CRC) is unclear. We studied CD163 in the tumor microenvironment and circulation of patients with CRC in relation to clinicopathological parameters. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum sCD163 levels and multiparameter flow cytometry was used to study the peripheral blood monocytes and their CD163 expression in CRC patients (N = 78) and healthy donors (N = 50). The distribution of tumor-associated macrophages (TAMs) was studied in primary colorectal tumors with multiplex immunofluorescence. We showed that CRC patients with above-median sCD163 level had a shorter overall survival (OS, p = 0.035) as well as disease-free survival (DFS, p = 0.005). The above-median sCD163 remained significantly associated with a shorter DFS in the multivariate analysis (p = 0.049). Moreover, a shorter OS was observed in CRC patients with an above-median total monocyte percentage (p = 0.007). The number and phenotype of the stromal and intraepithelial TAMs in colorectal tumors were not associated with clinical outcome. In conclusion, sCD163 and monocytes in the circulation may be potential prognostic biomarkers in CRC patients, whereas TAMs in the tumor showed no association with clinical outcome. Thus, our results emphasize the importance of the innate systemic immune response in CRC disease progression.

Download Full-text

The Milan System for Reporting Salivary Gland Cytopathology: Assessment of Cytohistological Concordance and Risk of Malignancy

Acta Cytologica ◽

10.1159/000510720 ◽

2020 ◽

pp. 1-13

Author(s):

Shilpy Jha ◽

Suvradeep Mitra ◽

Suvendu Purkait ◽

Amit Kumar Adhya

Keyword(s):

Salivary Gland ◽

Predictive Value ◽

Malignant Tumors ◽

Minor Salivary Gland ◽

Treatment Protocol ◽

Needle Aspiration ◽

Histopathological Diagnosis ◽

Wide Range ◽

Risk Of Malignancy

Introduction: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was proposed by the American Society of Cytopathology and the International Academy of Cytology to bring uniformity in the reporting system and the treatment protocol. A wide range of risk of malignancy for each category has been reported by various authors by applying the system. Aim: We intend to study the cytohistological concordance and the ROM for each of the diagnostic categories of the Milan system. Materials and Methods: The study included 292 cases of fine-needle aspiration cytology (FNAC) of salivary gland lesions over a period of 3 years. The diagnosis of these cases was reclassified into the 6 categories of the Milan system. The cytohistological concordance and ROM for each category of the Milan system were calculated based on the clinical and histopathological follow-up. Results: The patients’ age ranged from 3 to 81 years with the mean of 42.65 ± 16.3 years. The cases included 189 (64.7%) parotid, 82 (28.1%) submandibular, and 21 (7.2%) cases of minor salivary gland swellings. Follow-up histopathological diagnosis for 102 cases was available. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated to be 64.28, 97.01, 90, 86.67, and 87.37%, respectively. After reclassification, the number of cases in each category was as follows: category I: 31 (10.62%), category II: 80 (27.4%), category III: 2 (0.68%), category IVA: 143 (48.97%), category IVB: 1 (0.34%), category V: 13 (4.45%), and category VI: 22 (7.53%). The calculated ROM was as follows: category I: 42.86%, category II: 26.67%, category III: 100% category IVA: 10.17%, category IVB: 0%, category V: 71.42%, category VI: 100%. Conclusion: FNAC is an excellent procedure to differentiate benign from malignant tumors, and MSRSGC is a useful system for risk assessment and deciding the further treatment protocol. Our findings also suggest that in addition to the surgical follow-up, inclusion of the clinical and radiological follow-up may be a better strategy for calculation of ROM, especially for categories I and II.

Download Full-text

Histological Classification and Immunohistochemical Study of Feline Colorectal Epithelial Tumors

Veterinary Pathology ◽

10.1177/0300985820974279 ◽

2020 ◽

pp. 030098582097427

Author(s):

Mizuho Uneyama ◽

James K. Chambers ◽

Ko Nakashima ◽

Kazuyuki Uchida ◽

Hiroyuki Nakayama

Keyword(s):

Bowel Resection ◽

Immunohistochemical Study ◽

Undifferentiated Carcinoma ◽

Nuclear Accumulation ◽

Colorectal Tumors ◽

Kras Mutations ◽

Tubule Formation ◽

Ki67 Labeling Index ◽

Node Metastasis ◽

Epithelial Tumors

Among 113 feline gastrointestinal epithelial tumors diagnosed between 2006 and 2019, 78 (69%) were detected in the colorectum. Fifty colorectal tumors were selected for further pathological evaluations, of which 9 (18%) were histopathologically diagnosed as adenomas and 41 (82%) as carcinoma. The carcinomas included 33 tubular adenocarcinomas (TAC), 5 tubulovillous adenocarcinomas (TVAC), 2 mucinous adenocarcinomas, and 1 undifferentiated carcinoma. Histopathologically, TAC frequently showed vascular invasion (17/33 cases, 52%). In TAC cases, serosal infiltration (13/15 cases, 87%) and lymph node metastasis (8/9 cases, 89%) were common in bowel resection and lymphadenectomy samples, respectively. Immunohistochemically, the tumor cells of most cases were positive for cytokeratin (CK) 20 (50/50 cases, 100%) and CDX2 (48/50 cases, 96%). Focal immunopositivity for CD10 (11/50 cases, 22%) and CK7 (15/50 cases, 30%) was observed irrespective of the histological subtype. Only a few cases showed diffuse nuclear accumulation of β-catenin (2/50 cases, 4%) and p53 (5/50 cases, 10%). A lack of tubule formation, female sex, and low CDX2 labeling were statistically associated with carcinoma compared to adenoma (ρ = 0.615, P < .001; ρ = 0.279, P = .050; and ρ = −0.265, P = .063, respectively). Other features, including mucin profiles, Ki67 labeling index, and accumulation of β-catenin and p53, were not associated with malignancy. A sequence analysis revealed KRAS mutations in 3/7 TAC cases. These results suggest that KRAS mutations—rather than excessive Wnt/β-catenin signaling and the inactivation of TP53—contribute to the tumorigenesis of feline colorectal carcinoma.

Download Full-text

A data-driven approach to a chemotherapy recommendation model based on deep learning for patients with colorectal cancer in Korea

BMC Medical Informatics and Decision Making ◽

10.1186/s12911-020-01265-0 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Jin-Hyeok Park ◽

Jeong-Heum Baek ◽

Sun Jin Sym ◽

Kang Yoon Lee ◽

Youngho Lee

Keyword(s):

Colorectal Cancer ◽

Deep Learning ◽

Decision Support ◽

Cancer Treatment ◽

Clinical Decision Support ◽

Treatment Guidelines ◽

Treatment Protocol ◽

Clinical Decision ◽

Actual Data ◽

Nccn Guidelines

Abstract Background Clinical Decision Support Systems (CDSSs) have recently attracted attention as a method for minimizing medical errors. Existing CDSSs are limited in that they do not reflect actual data. To overcome this limitation, we propose a CDSS based on deep learning. Methods We propose the Colorectal Cancer Chemotherapy Recommender (C3R), which is a deep learning-based chemotherapy recommendation model. Our model improves on existing CDSSs in which data-based decision making is not well supported. C3R is configured to study the clinical data collected at the Gachon Gil Medical Center and to recommend appropriate chemotherapy based on the data. To validate the model, we compared the treatment concordance rate with the National Comprehensive Cancer Network (NCCN) Guidelines, a representative set of cancer treatment guidelines, and with the results of the Gachon Gil Medical Center’s Colorectal Cancer Treatment Protocol (GCCTP). Results For the C3R model, the treatment concordance rates with the NCCN guidelines were 70.5% for Top-1 Accuracy and 84% for Top-2 Accuracy. The treatment concordance rates with the GCCTP were 57.9% for Top-1 Accuracy and 77.8% for Top-2 Accuracy. Conclusions This model is significant, i.e., it is the first colon cancer treatment clinical decision support system in Korea that reflects actual data. In the future, if sufficient data can be secured through cooperation among multiple organizations, more reliable results can be obtained.

Download Full-text

Somatic deletion of KDM1A/LSD1 gene is associated to advanced colorectal cancer stages

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-206128 ◽

2019 ◽

Vol 73 (2) ◽

pp. 107-111 ◽

Cited By ~ 2

Author(s):

Ruth Ramírez-Ramírez ◽

Melva Gutiérrez-Angulo ◽

Jorge Peregrina-Sandoval ◽

José Miguel Moreno-Ortiz ◽

Ramon Antonio Franco-Topete ◽

...

Keyword(s):

Colorectal Cancer ◽

Gene Deletion ◽

In Situ Hybridisation ◽

P Value ◽

Histopathological Diagnosis ◽

Fluorescence In Situ Hybridisation ◽

Tissue Samples ◽

Copy Numbers ◽

Gene Copies ◽

Advanced Stages

AimsKDM1A/LSD1 and ZNF217 are involved in a protein complex that participates in transcriptional regulation. ZNF217 has been analysed in numerous cancers and its amplification has been associated with advanced stages of disease; however, a similar role for KDM1A/LSD1 has not been uncovered. In this study, we estimated the number of KDM1A/LSD1 and ZNF217 gene copies in tissue samples from patients diagnosed with colorectal cancer (CRC), as well as its association with clinicopathological features in patients with CRC.MethodsParaffin-embedded tumour samples from 50 patients with CRC with a histopathological diagnosis of CRC were included. The number of copies of KDM1A/LSD1 and ZNF217 genes was determined by fluorescence in situ hybridisation (FISH). We also analysed the association between copy numbers of selected genes and clinicopathological data based on multivariate analysis.ResultsDeletion of the KDM1A/LSD1 gene occurred in 19 samples (38%), whereas ZNF217 gene amplification was identified in 11 samples (22%). We found a significant association between lymph node metastasis or advanced tumour stage and KDM1A/LSD1 gene deletion (p value=0.0003 and p value=0.011, respectively).ConclusionsKDM1A/LSD1 gene deletion could be considered a novel prognostic biomarker of late-stage CRC.

Download Full-text