MVP Expression Facilitates Tumor Cell Proliferation and Migration Supporting the Metastasis of Colorectal Cancer Cells

Cancer cells show significant dysregulation of genes expression, which may favor their survival in the tumor environment. In this study, the cellular vault’s components MVP (major vault protein), TEP1 (telomerase-associated protein 1) and vPARP (vault poly(ADP-ribose) polymerase) were transiently or completely inhibited in U2OS cells (human bone osteosarcoma epithelial cells) to evaluate their impact on the cell proliferative and migratory capacity as well as on the development of their resistance to the drug vinorelbine. Comparative analysis of MVP protein expression level in normal colon tissue, primary colorectal tumor, and metastasis showed that the expression of this protein does not increase significantly in the primary tumor, but its expression increases in metastatic cells. Further comparative molecular analysis using the whole transcriptome microarrays for MVP-positive and MVP-negative cells showed that MVP is involved in regulating proliferation and migration of cancer cells. MVP may facilitate metastasis of colon cancer due to its impact on cell migration. Moreover, two vault proteins, MVP and TEP1, contribute the resistance to vinorelbine, while vPARP does not.

Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

Rapid screening for individualized chemotherapy optimization of colorectal cancer: a novel conditional reprogramming technology-based functional diagnostic assay.

In vitro patient tumor models such as patient-derived organoids (PDO) and conditionally reprogrammed (CR) cell culture are important for translational research and pre-clinical drug testing.In this study we present a personalized drug sensitivity test for late stage, potentially operable colorectal cancer (CRC) using patient-derived primary cell culture based on a new generation CR technology. We explored the clinical feasibility of using CR-based primary cell culture system to guide CRC chemotherapy, and established the correlation between in vitro drug sensitivity and patient clinical response.Our novel CR platform (termed i-CR) can be used to propagate primary colorectal tumor cells that represent individual patient tumors effectively by keeping the clonal heterogeneity and comparable drug responses.Therefore, our platform can be used to test and optimize therapeutic regimens pre-clinically, study cancer cell biology, and model tumor re-emergence to identify new targeted therapeutics from an effective personalized medicine standpoint.

Mismatch repair status between primary colorectal tumor and metastatic tumor, a retrospective consistent study

Objectives Mismatch repair (MMR) and Microsatellite instability (MSI) are critical when considering immunotherapy and chemotherapeutic drugs an option for patients with colorectal cancer (CRC). We investigated the consistence of MMR status as well as MSI between primary CRC and metastatic tumor to see if the expression of four MMR proteins and the status of MSI are congruent in primary tumor and metastatic tumor. With the results of the study and future more relevant studies, the sites of MMR testing may be more precise for individualized treatment. Study design Patients with clear diagnosis of sporadic CRC and distal organ metastasis were identified from a prospectively established database. The status of MMR and MSI was evaluated by immunohistochemistry (IHC) and Polymerase Chain Reaction (PCR) respectively of synchronously obtained tissue samples. Results Forty patients with complete clinical date were enrolled. For primary tumor, 36/40 samples were tested as MMR-proficient (pMMR) and 4 were MMR-deficient (dMMR). For metastatic samples, 30 samples were tested as pMMR while 10 samples were dMMR. Six out of forty patients were tested as inconsistent status of MMR and MSI. After statistical analysis, the expression status of MMR was not statistically significant between primary and metastatic tumors (P=0.1405, larger than 0.05). Conclusion Based on our samples, the status of MMR between primary CRC and metastatic tumor was consistent, thus test of MMR status can be performed at both sites. However, due to the limited samples enrolled in our study, the results should be interpreted carefully.

Perianal Pagetoid Intraepithelial Carcinoma

Extramammary Paget disease (EMPD) involving the perianal region is rare and challenging to manage. Primary EMPD involves stand-alone noninvasive lesions within the epidermis, while secondary EMPD involves phenotypically similar lesions derived from separate underlying malignancies. Differentiating between primary and secondary EMPD is challenging when no underlying malignancies are detected during workup. Continued reporting of perianal EMPD cases is encouraged so that risk stratification can be improved and patients can be managed with an appropriate level of aggressiveness. Herein, we report the case of a 74-year-old woman who chose aggressive surgical management after being diagnosed with perianal pagetoid intraepithelial carcinoma from a suspected occult underlying primary colorectal tumor.