Nibrin expression in oral squamous cell carcinoma: association with clinicopathological parameters

Aim: The present study sought to discover the role of Nibrin protein in 100 patients with oral squamous cell carcinoma (OSCC) and its potential relationship with clinicopathological parameters.Methods: Nibrin expression was evaluated immunohistochemically using the modified H-score method.Results: The present study included 20% of patients with stage I disease, 22% of patients with stage II disease, 18% of patients with stage III disease, and 40% of patients with stage IV disease. Nibrin showed a significant positive correlation with moderately/poorly differentiated tumor tissues (P = 0.028), while significant inverse correlation of Nibrin expression was observed with tumor size (P = 0.018) and tumor stage (P = 0.039). Further, using univariate survival analysis it was observed that strong Nibrin expression was significantly associated with disease relapse in early stage OSCC patients (P = 0.049).Conclusion: Thus, the present study revealed that Nibrin could be used as a prognostic marker in patients with early stage OSCC

Influence of thymidylate synthase expression on survival in patients with colorectal cancer

Background: Thymidylate synthase (TS) plays a critical role in nucleotide metabolism and is an important target for 5-fluorouracil (5-FU), the standard chemotherapeutic drug for treatment of colorectal cancer (CRC). Aims and Methods: The present study aimed to evaluate TS variable number tandem repeat sequences (VNTR) polymorphism by polymerase chain reaction and TS protein expression by immunohistochemistry and its association with clinicopathological parameters in untreated CRC patients (n = 100). Further, the prognostic and predictive role of TS has been evaluated. Results: For TS VNTR polymorphism, the observed frequencies of 2R/2R, 2R/3R, and 3R/3R genotypes were 22%, 51%, and 27%, respectively. When immunohistochemical localization was studied, cytoplasmic staining for TS was observed in 70% of patients. A significant inverse correlation was noted between TS protein expression and tumor, node, metastasis staging (P = 0.027), Dukes' staging (P = 0.039), and lymph node status (P = 0.012) of CRC patients. However, there was no significant correlation between TS VNTR polymorphism and TS protein expression. On survival analysis, a significantly shorter overall survival (OS) was seen in CRC patients with negative protein expression (P = 0.031). Moreover, the subgroup of CRC patients treated only with surgery also showed a trend of poor OS in patients with negative TS protein expression (P = 0.058). However, neither TS polymorphism nor its protein expression was able to predict relapse-free survival. Conclusion: Negative TS protein expression may be related to unfavorable clinical outcome in CRC patients. However, further studies in a larger set of patients are necessary to better assess TS as a prognostic and predictive marker for 5-FU response in CRC patients

ERCC1 expression in patients with colorectal cancer: a pilot study

Aim: Excision repair cross complementation group 1 (ERCC1) has a key role in enhanced DNA damage repair caused by oxaliplatin-based therapy and may lead to resistance of these platinum drugs in colorectal cancer (CRC) patients. Hence, the present preliminary study aimed to explore the role of ERCC1 C/T polymorphism at codon 118 as well as its immunoreactivity in patients with primary CRC. Methods: ERCC1 polymorphism was studied using PCR-RFLP and ERCC1 protein expression was examined by immunohistochemistry in 50 CRC patients. Results: ERCC1 codon 118 C/T polymorphism analysis reported the predominance of C/T (52%) genotype as compared to C/C (38%) and T/T (10%) genotypes. Furthermore, 72% of patients showed positive ERCC1 protein expression. Significant correlation was not observed between clinicopathological parameters and ERCC1 polymorphism, while ERCC1 protein expression significantly correlated only with tumor site (colon vs. rectum) (P = 0.046). Further, the present study failed to demonstrate the role of ERCC1 C118T polymorphism or protein expression as useful prognostic markers in CRC patients. Conclusion: ERCC1-positive protein expression may be a useful marker for rectal cancer patients. However, further evaluation in a larger set of CRC patients is required to better understand the role of ERCC1

Aleukemic granulocytic sarcoma and leukemia cutis: A report of two rare cases and review of literature

Granulocytic sarcoma (GS), also called myeloid sarcoma is an extramedullary tumor of the immature granulocytic cells. It is a rare entity and mostly accompanied by acute myeloid leukemia (AML). Very rarely, it is detected before clinical signs of leukemia or other diseases. When the bone marrow biopsy reveals no other hematologic malignancies, the GS is described as aleukemic, primary or isolated. Here, we report two rare cases, one of which presented as aleukemic GS of lymph nodes with aleukemic leukemia cutis, and the other with aleukemic GS of lung. Both cases posed diagnostic dilemma in view of their atypical presentations and site of involvement. Final diagnosis was made by immunohistochemistry (IHC). Both patients were treated with standard induction chemotherapy for AML. One patient had relapsed on treatment and was further treated with only 6-thioguanine leading to complete remission. Our cases emphasize the importance of early suspicion and use of IHC in diagnosis of aleukemic GS and also potential role of oral thioguanine alone in relapsed cases not eligible for hematopoietic stem cell transplant

Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer

Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4–82.6), 88.1% (95%-CI, 85.7–90.4), 93.4% (95%-CI, 91.1–95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18–0.41); p p P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered