Utility of Prognostic Scoring System Based on Histomorphological Parameters in Low-grade Colorectal Carcinoma

Introduction: Colorectal Carcinoma (CRC) is the third most common cancer worldwide. Percentage of gland formation is the only valid parameter for histologic grading of CRC . Tumour budding and Tumour-infiltrating Lymphocytes (TILs) are emerging prognostic factors in CRC. In recent years high grade CRC has become subject to more precise molecular grading strategies. However low grade cases show in homogenous outcome due to still insufficient categorization. The focus of this study is to determine whether the combination of amount of gland formation, budding, and TILs will allow us to further characterize large in homogenous group of WHO low-grade cases into prognostically significant subgroups. Aim: To estimate the significance of tumour budding and TILs in low-grade CRC and to categorise low-grade CRC into prognostic subgroups taking into account 3 histologic parameters-gland formation, tumour budding and TIL. Materials and Methods: This was a descriptive cross-sectional study done in the Department of Pathology, MES Medical College, Malappuram, Kerala, India. It was an ambispective study (retrospective from January 2015 to December 2021 and prospective from December 2021 to March 2022) which analysed 105 World Health Organization (WHO) low-grade CRC cases. The demographic data of the patients was collected and histopathological assessment of tumour grade, pT, pN, lymphovascular invasion (LVI), Tumour-infiltrating lymphocytes (TIL) and tumour budding (TB) was done on Haematoxylin and Eosin (H&E) stained sections. A morphology-based risk score was developed taking into account 3 parameters- percentage of gland formation, budding, and TIL. For each parameter, 1 to 2 points were given, resulting in a sum score, dividing the CRC cases into a low-, an intermediate-, and a high-risk group. Statistical analysis was performed using SPSS 25. The results were expressed as numbers and percentage. Pearson Chi-square test was used to test the relationship. Results: In the present study degree of budding significantly associated with pT stage (p=0.02), pN stage (p=0.042) and LVI (p=0.038). TIL also differed significantly with pT (p=0.001) pN (p=0.042) and LVI (p=0.004). Applying the prognostic scoring to 105 cases, 33 (31.4%) cases showed high score, 30 (28.6%) cases were of intermediate score and 42 (40%) cases showed low score. The 3 groups differs significantly with pT (0.027), pN (0.035) and LVI (0.015). Conclusion: The present study showed combining different morphological parameters of tumour and tumour environment can help to further subdivide CRC into prognostically significant subgroups

Functional Dissection of the Dominant Role of CD55 in Protecting Vesicular Stomatitis Virus against Complement-Mediated Neutralization

The human complement system is an important part of the innate immune system. Its effector pathways largely mediate virus neutralization. Vesicular stomatitis virus (VSV) activates the classical pathway of the complement, leading to virus neutralization by lysis. Two host-derived membrane-associated regulators of complement activation (RCA), CD55 and CD46, which are incorporated into the VSV envelope during egress, confer protection by delaying/resisting complement-mediated neutralization. We showed previously that CD55 is more effective than CD46 in the inhibition of neutralization. In this study, we identified that, at the protein level, VSV infection resulted in the down-regulation of CD46 but not CD55. The mRNA of both the RCAs was significantly down-regulated by VSV, but it was delayed in the case of CD55. The immunoblot analysis of the levels of RCAs in the progeny virion harvested at three specific time intervals, points to an equal ratio of its distribution relative to viral proteins. Besides reconfirming the dominant role of CD55 over CD46 in shielding VSV from complement, our results also highlight the importance of the subtle modulation in the expression pattern of RCAs in a system naturally expressing them