Simplified and Optimized Immune Score for Colorectal Cancer Microenvironment.

BACKGROUND/AIM: Immunoscore (IS) is an important evaluation method for the tumor immune microenvironment (TIME); however, formal IS analysis requires designated reagents and a specific digital pathology software and image data analysis. This study aimed to investigate whether simplified IS (s-IS) can substitute formal IS upon modifying the location of the assessment of the numbers of immune cells and verify that the addition of T cell subset markers to s-IS can enhance the prognostic impact in patients with colorectal cancer (CRC). PATIENTS AND METHODS: A total of 82 CRC cases were included in this study. Immunohistochemical analysis was performed using CD3/CD8/CD45RO/FOXP3 on tissue specimens; the expression levels were calculated in the center and perimeter of the tumors using digital pathology. The clinical prognostic significance of the expression of these markers was investigated by concordance index comparison according to their location of assessment and combinations. RESULTS: In the univariate analysis, the CD3, CD8, and FOXP3 levels were significant prognostic factors. Moreover, for each T cell subset marker, the assessment of each T cell subset marker at the tumor perimeter had a stronger prognostic power than that in the tumor center. The modified s-IS (s-IS plus FOXP3 evaluation) was an independent prognostic factor for recurrence-free survival and overall survival through multivariate analysis and demonstrated the best prognostic power compared to other T subset marker combinations. CONCLUSION: In CRC, TIME evaluation could be simplified by assessing CD3- and CD8-positive T cells in the perimeter of the tumor, and additional FOXP3 evaluation would empower the ability of s-IS evaluation in prognostic assessment.

Y­box­binding protein 1 inhibits apoptosis and upregulates EGFR in colon cancer.

Y­box­binding protein 1 (YB­1) is a DNA/RNA­-binding protein and an important transcription and translation factor in carcinogenesis. However, the biological function and molecular correlation of YB­1 in colorectal cancer are not fully understood. The aim of the present study was to determine the significance of YB­1 expression and its biological role in colorectal cancer. Cell proliferation, migration and apoptosis were examined upon knockdown of YB­1 expression in different colon cancer cell lines that had different genetic backgrounds. Since the properties of different colon cancer cell lines with specific RAS/RAF gene mutations downstream epidermal growth factor receptor (EGFR) may differ from wild­type colorectal cancer, it is critical to study the role of YB­1 with respect to the mutational status of RAS. The results indicated that the suppression of YB­1 decreased cell proliferation (P<0.05) and migration (P<0.05) regardless of the status of RAS/RAF in the HT29, HCT116 and CaCo2 cell lines. In contrast, YB­1 knockdown altered the expression of apoptosis­related genes and the expression of EGFR was detected in the cell lines expressing wild­type RAS/RAF but not in those expressing mutated RAS/RAF. These results indicated that YB­1 plays an important role in cell proliferation, migration, apoptosis and EGFR expression in colorectal cancer. Furthermore, apoptosis and EGFR expression may be affected by the mutational status of RAS/RAF and controlled through YB­1.

[A Case of Chemotherapy-Induced Hyperammonemic Encephalopathy in a Patient with Metastatic Colon Cancer].

A 70-year-old man was diagnosed with colon cancer with multiple liver metastases.He was administered modified FOLFOX6 plus panitumumab as first-line chemotherapy.He showed consciousness disturbance on the 3rd day during the 8 cycle and was hospitalized urgently.We diagnosed him with 5-FU-induced hyperammonemia.Administration of branchedchain amino acid preparation improved his consciousness disturbance.After changing the regimen of chemotherapy to another one containing oral fluoropyrimidine, the recurrence of hyperammonemic encephalopathy was not found.

[A Case of Postoperative Recurrence of Rectal Cancer in Which Desensitization Therapy Was Effective against Oxaliplatin Allergy in L-OHP].

The case involved a 44-year-old man who underwent intersphincteric resection and lateral lymph node dissection for rectal cancer. Pathological diagnosis revealed a well-differentiated adenocarcinoma comprising KRAS wild type, and pT2N0M0 (pathological Stage I). CapeOX (capecitabine plus oxaliplatin[L-OHP]), and bevacizumab therapy was initiated because of local recurrence. Although a partial response (PR) was observed, the therapy was terminated after 6 courses because of the development of hand-foot syndrome. FOLFIRI and cetuximab therapy was initiated after cancer recurrence was observed during a follow up. As the therapeutic efficiency is characterized by stability (stable disease: SD), and the tumor reduction effect observed was not sufficient, we performed an abdominoperineal resection to achieve local control. However, a left hydronephrosis occurred due to the pelvic recurrence, necessitating the emergency hospitalization of the patient. Because resistance to L-OHP was not confirmed, mFOLFOX6 and bevacizumab therapy was introduced in hopes of the effect of the former. As Grade 2 allergy (erythema) appeared immediately after the L-OHP was administered during the 3 courses, treatment was discontinued. We the reinitiated the treatment along with the desensitization therapy from the 4 courses. A total of 27 courses of mFOLFOX6 and bevacizumab therapy were administered until the state of disease progression (progression disease: PD) was determined. PR was defined as the best therapeutic efficiency. In some cases, discontinuation of treatment is necessary as observed in the present case due to the onset of L-OHP allergies, even if the overall effect of the treatment is expected to be good. Our case is essentialas it demonstrates the successfulness of desensitization therapy for L-OHP allergies.