Significant association of MCP1 rs1024611 and CCR2 rs1799864 polymorphisms with colorectal cancer and liver metastases susceptibility and aggressiveness: A case-control study.

BACKGROUND: The MCP-1/CCR2 axis is one of the major chemokine signaling pathways that play a crucial role in the tumor microenvironment and has been involved in triggering various tumor progression mechanisms, such as increasing the immunosuppressive cells recruitment and promoting tumor cell proliferation and invasiveness. AIM: The current study investigated the association of MCP1 (rs1024611) and CCR2 (rs1799864) genes variants with the risk as well as prognosis of colorectal cancer (CRC) and colorectal liver metastases (CRLM). SUBJECTS AND METHODS: A retrospective cohort study involved 408 patients (284 CRC and 124 CRLM), and 284 healthy control was conducted. Genotyping of selected polymorphisms was performed by PCR-RFLP assays and confirmed by microchip and capillary electrophoresis. RESULTS: The results highlighted a positive association between MCP1 rs1024611 (non-AA) and CCR2 rs1799864 (GA) genotypes with increased CRC and CRLM risk. Correlation between SNPs and clinicopathological characteristics revealed a positive association between MCP1 rs1024611 and CCR2 rs1799864 (dominant model) and CRC poor prognosis features. Kaplan-Meier survival analysis revealed a significant association between MCP1 rs1024611 non-AA carriers and decreased survival rate. Neoadjuvant treatment showed an improvement in CRC and CRLM survival rates among carriers of MCP1 and CCR2 wild-type genotype. FOLFIRI chemotherapy exhibits reduced survival rates for patients who carried mutated genotypes of MCP1 and CCR2 polymorphisms. CONCLUSION: Considering our results, we suggest That both MCP1 and CCR2 polymorphisms may constitute independent factors for CRC and CRLM occurrence and can be helpful targets for an efficient therapeutic approach.

Mucinous breast carcinoma with neuroendocrine differentiation: Case report.

Mucinous carcinoma of the breast is rare representing 2% of all breast carcinomas. It can be classified as either a pure or a mixed type. Pure mucinous breast carcinoma has a less aggressive behavior compared with mixed breast mucinous carcinoma. The latter shows frequent neuroendocrine differentiation.

Puzzling hepatic tumor: Epithelioid angiomyolipoma.

Hepatic epithelioid angiomyolipomas are uncommon mesenchymal neoplasms. They are difficult to diagnose by imaging, especially when the fatty component is scant or absent. The gold standard for the diagnosis is histologic examination coupled with an immunohistochemical study. Positive HMB45 immunostaining of the myoid cells is a major diagnostic feature.

A rare and distinct bilateral ovarian tumor: Carcinosarcoma.

Carcinosarcomas are aggressive biphasic neoplasms composed of high-grade, malignant, epithelial, and mesenchymal elements. They usually occur in the uterus and rarely involve the ovaries. Only 10% of them are bilateral. Their diagnosis relies on histological examination coupled with immunohistochemistry.

Mixed fibrolamellar hepatocellular carcinoma.

Pure and mixed fibrolamellar hepatocellular carcinomas display distinct clinical presentations and epigenetic backgrounds leading to different prognoses and as such may be regarded as separate clinical entities.

A rare and distinct hepatic tumor: Hepatocholangiocarcinoma.

The rare histological features of hepatocholangiocarcinoma require a thorough sampling of the surgical specimen and the application of immunohistochemical techniques to confirm the diagnosis.

Mucinous cystic neoplasm of the liver mimicking a hydatid cyst.

Misdiagnosis of mucinous cystic neoplasms of the liver may have serious consequences due to their premalignant potential. A thorough understanding of their characteristic features and a high index of suspicion are mandatory (Mod Pathol, 24, 2011, and 1079).

Clinicopathological characteristics and mutational profile of KRAS and NRAS in Tunisian patients with sporadic colorectal cancer

Background/aim: Colorectal cancer (CRC) is a major public health problem worldwide and in Tunisia due to its increasing rate of incidence. KRAS and NRAS mutations have become a pivotal part of CRC diagnosis, given their association to treatment resistance with antiepidermal growth factor receptor (EGFR) monoclonal antibodies. In this study, we aimed to screen for mutations in KRAS and NRAS genes in Tunisian patients with CRC and explore their correlations with clinicopathological features. Materials and methods: AmoyDx KRAS and NRAS mutation real-time PCR kits were used to screen for mutations in KRAS (exon 2) and NRAS (exons 2, 3, and 4) in 96 CRC tumors. Results: KRAS exon 2 mutations were found in 41.7% (40/96) of the patients. Codon 12's most abundant mutations were G12D and G12V, followed by G12A, while G13D is the predominant mutation in codon 13. KRAS exon 2 mutations were associated with older patients (P = 0.029), left-sided tumors (P = 0.037), and greater differentiation (P = 0.044). The prevalence rate of NRAS mutations was 7.3%, mostly in exon 2. These mutations were associated with early stages of the disease (P = 0.039) and the absence of lymph node metastasis (P = 0.045). Conclusion: It can be inferred from this study that Tunisian CRC patients have a similar frequency of KRAS and NRAS mutations compared to those observed in other populations. Consequently, screening for KRAS and NRAS mutations is crucial for the orientation of therapies and the selection of appropriate candidates, while also helping to avoid unnecessary toxicity and increased costs for patients.

MUC1 and MUC5AC implication in Tunisian colorectal cancer patients

Background/aim: Mucins, such as MUC1 and MUC5AC, are known for their protective and moisturizing role in intestinal epithelium. Their expression is tightly controlled given their essential role in normal tissue homeostasis, whereas their deregulation leads to chronic inflammation, and even cancer. This study aimed to assess the expression profiles of MUC1 and MUC5AC and their implications in colorectal carcinogenesis. Materials and methods: A retrospective study of 202 patients who underwent colorectal cancer (CRC) surgery was conducted. The expression of MUC1 and MUC5AC was investigated by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR). Statistical analysis of mucin expression pattern, as well as the clinicopathological criteria of the patients, was performed using the chi-square test, survival curves were plotted using the Kaplan­Meier product-limit method, and differences between the survival curves were tested using the log-rank test. Results: The expression of both mucins was abnormally high in the tumor tissues for both mRNA and protein. MUC1 expression was correlated with advanced cancer stages and lymph node metastases for both the mRNA (P < 0.016 and P < 0.002, respectively) and protein level (P < 0.006 and P < 0.001, respectively). However, MUC5AC expression did not pinpoint any significant association between the clinicopathological criteria, but patients who expressed MUC5AC showed an increase in overall survival (P < 0.009). Conclusion: The expression of MUC1 might be a poor prognostic biomarker in CRC and could play a role in tumor transformation and metastasis. However, MUC5AC expression might be a good prognostic in the Tunisian cohort.

[CD10 expression in stromal cells of patients with breast cancer: a poor prognostic marker]. / Expression stromale de CD10 dans les cancers du sein: marqueur de mauvais pronostic.

INTRODUCTION: markers in breast cancer stem cells, such as cluster of differentiation 10 (CD10), would be correlated with invasive and metastatic potential of several types of cancer, contributing to tumor growth and metastases. In patients with breast cancer, its prognostic value is still controversial, given the discrepancy of results. The purpose of the study was to study CD10 expression in stromal cells of patients with breast cancer as well as to evaluate the prognostic value of this expression. METHOD: we conducted a retrospective, descriptive and prognostic study. It involved 57 patients with invasive cancer of no special type, whose data were collected in the Department of Pathological Anatomy at the Mongi Slim Hospital over a 38-month period. CD10 expression was studied immunohistochemically and interpreted by semi-quantitative scoring system based on three categories with thresholds of 10 and 30%. RESULTS: the average age of patients was 56.4 years. Twenty-eight patients (49%) had labeled CD10 stromal, half of patients had a score of 1 (low) and the other half had 2 (high). This labeling significantly reduced recurrence-free survival (p=0.001). However, it had no influence on overall survival (p=0.84). The correlation study showed that CD10 expression in stromal cells was significantly correlated with 12 poor prognostic factors in patients with breast cancer. CONCLUSION: CD10 expression in stromal cells of invasive breast cancer is a poor prognostic factor, predictive of poor survival without recurrence and associated with a high invasive and metastatic potential.

Primary neuroendocrine tumour of the common hepatic duct: An unexpected Klatskin-like lesion.

The biliary system is an uncommon location for neuroendocrine tumours (NETs), and within this system, the common hepatic duct is an even more rare site for NETs. Clinical and radiological presentations are challenging because these tumours may be preoperatively confused with Klatskin-like lesions. Here we report a well-differentiated grade 2 NET arising from the common hepatic duct in a 64-year-old female. Curative surgery was performed, and no evidence of recurrent disease was observed at the 2-months follow-up.

OBJECTIVE MULTI-STATION CLINICAL EVALUATION IN PATHOLOGICAL ANATOMY. CRITICAL ANALYSIS AND PERCEPTION.

BACKGROUND: Multi-station objective clinical evaluation (MSOCE) is an equitable and genuine formative and normative assessment tool that is deemed relevant to its effectiveness, reliability and validity in clinical evaluation. However, no experience with its application in pathological anatomy has been published. AIM: To carry out a critical analysis and a perceptual study of the MSOCE in pathological anatomy in medical students. METHODS: This was a cross-sectional, multicenter prospective study in which we developed and tested a MSOCE on 32 medical students of the 1st year of the second cycle of medical studies. Docimological analysis of the 12 stations and the 28 questions of the different stations was done by the file "AnItem.xls". RESULTS: The mean total score obtained at the MSOCE was 36.2/50 (range : 29 to 41). The majority of stations were of acceptable difficulty (92%) and of poor discrimination (92%). The majority of questions were easy (57%) with poor discrimination (75% of the total questions). One question on 28 was "ideal", 4%. The MSOCE had a large heterogeneity (average Cronbach alpha of 0.29), and discriminated well between the average students (platykurtic, left-spread, negatively asymmetric distribution curve). The perception analysis showed that 27 students (84%) were satisfied with the OMSCE and thought that it was close to the reality of the clinical training. CONCLUSION: The OMSCE tested was easy and discriminated mostly between average students. It was well perceived by the students and close to the reality of the clinical training. Ongoing analysis will further improve the quality of MSOCE.

Follicular carcinoma arising from struma ovarii. A case report.

Struma ovarii is a monodermal variant of ovarian teratoma. Thyroid-type carcinoma arising in struma ovarii is rare. The most common type is papillary carcinoma, followed by typical follicular carcinoma. A 75-year-old hypertensive patient consulted for the sensation of a painless pelvic mass that has been progressing for six months. The abdominopelvic ultrasound showed a right lateralized abdominopelvic mass measuring 14x13x8 cm with a solid and cystic double component. The patient underwent a unilateral right adnexectomy. Grossly, the tumor was encapsulated and lobulated. On cut sections, it was solid brown whitish in color and gelatinous. On histological examination, it was formed of follicular structures of variable size filled with a dense colloid. From this goiter a malignant tumor proliferation arose, arranged in sheets, trabeculae and follicular structures, and the tumor cells were cubic or polyhedral moderately atypical with few mitotic figures. There were no papillary-like nuclear features. There was focal capsular and vascular invasion. Immunohistochemical study showed positive immunostaining of tumor cells with TTF1. Postoperative course was uneventful. The exact prognosis of thyroid-type carcinoma arising in struma ovarii is still unclear because of its rarity, inadequate follow-up, and the absence of consensus in diagnosis and treatment.

Clonal seborrheic keratosis: a rare skin tumor.

Seborrheic keratosis is a benign epidermal neoplasm, representing one of the most common skin tumors. Clonal seborrheic keratosis is one of the histological subtypes of this entity. It is an uncommon lesion which may resemble other benign or malignant lesion. We report a case of a 60-year-old woman presented with a 7 year history of a gradually growing, cutaneous lesion on her left arm. On physical examination, the lesion was elevated, well-circumscribed, measuring 5 cm in maximum diameter. The tumor was biopsied. Histopathological examination revealed the presence of well-defined nests of clear-looking or basaloid keratinocytes within an acanthotic epidermis, corresponding to the Borst-Jadassohn phenomenon. The tumor cells were small and monomorphic. We diagnosed this tumor as clonal seborrheic keratosis. Although surgical excision was recommended, our patient refused an operation. This case of clonal seborrheic keratosis is presented for its rarity and for differential diagnosis.

Protective role of vitamin E against cadmium induced oxidative stress into the rat liver.

INTRODUCTION: Cadmium (Cd) is a toxic heavy metal used in various industrial applications and therefore can cause, both by environmental or professional exposure, several damage in all body systems. The present study was developed to determine the toxic effect of high dose of Cd on the rat's liver as well as the putative protective effect of vitamin E. METHODS: During the experiment, rats were administrated Cd per orally (PO) (15mg/Kg bw) alone or associated with an intraperitonial (IP) injection of alphatocopherol (Vitamin E) (300mg/Kg / day) for three weeks. We analyzed the effect of vitamin E on Cd induced liver remodeling by hematoxylin-eosin staining (HE), and by the determination of the antioxidant profiles and lipid peroxidation in rats's livers. RESULTS: Data confirmed that high dose of cd induced a loss of the liver weight and a pro-oxidative state into hepatocytes characterized by increased malondialdehyde (MDA) and peroxidase (POD), no changes in catalase (CAT) and a decrease on the superoxide dismutase (SOD) activities. These disturbances may be explained by a decrease in the level of hepatic calcium (Ca). Co-treatment with Vitamin E, decreased MDA and POD activities, increased CAT and SOD activities and restored Ca level. All these corrections were accompanied by an improvement of the liver 's structure. CONCLUSION: Our results suggest that Cd induced an oxidative stress into rat liver and Vitamin E exerted antioxidant properties which can be mediated by the modulation of Ca level.

[Unexpected discovery of isolated osteochondroma in the pubic symphysis]. / Ostéochondrome solitaire de la symphyse pubienne de découverte fortuite.

Osteochondroma is the most common benign bone tumor. It usually affects the metaphyses of the long bones, in particular around the knee and the proximal humerus. It very rarely affects the pubic symphysis, usually with an atypical symptomatology. We here report the case of a 35-year old man in whom osteochondroma in the pubic symphysis encroaching on the iliopubic branch was fortuitously discovered. Radiological examinations as well as macroscopic and histological examination confirmed the diagnosis and the absence of signs of malignancy.

A disconcerting false gastric diverticulum mimicking malignancy.

Gastric diverticula are the most uncommon form of gastrointestinal diverticula. They can either be of true or false type with different pathogenesis. They may be very challenging to diagnose as symptoms are nonspecific and imaging can simulate a malignant lesion. We report an unusual case of pre-pyloric diverticulum in a 69-year-old man, leading to severe gastric obstruction with a poor general condition. As subsequent endoscopy and imaging were alarming and couldn't exclude malignancy, the patient underwent an antrectomy. The final diagnosis was made on pathological examination. We discuss, through this case, the clinical and pathological features of gastric diverticula with an emphasis on the pathogenesis of this rare entity and the risk of a malignant transformation.

Predictive factors for histological response to neo-adjuvant treatment in rectal cancers.

INTRODUCTION: The complete histological response represents the goal of neo-adjuvant treatment of locally advanced rectal cancer. This objective is a real challenge requiring the research of predictive factors for this response, from the perspective of targeted therapeutic strategies. The results of the various studies focused on these predictive factors are discordant. AIM: To seek a correlation between 7 prognostic factors tested in pre-therapy and the histological response to neo-adjuvant treatment. METHODS: A retrospective study involving 44 patients with locally advanced rectal adenocarcinoma who received neo-adjuvant radiotherapy or radiochemotherapy. The 7 prognostic factors studied were clinical (age and sex), radiological (tumor size and parietal invasion) and histological (histological grade, vascular and nerve invasion) features. The complete histological response was defined by Bateman's tumor grade m-RCRG 1 and the absence of lymph node metastases. RESULTS: A complete histological response was observed in 25% of cases (n = 11). In multivariate analysis, age> 60 years (OR: 1.14 and p = 0.028), male sex (OR: 21 and p = 0.045) and radiological wall invasion exceeding the subserosa (OR: 11 , 5 and p = 0.008) were significantly associated with the histological response. In contrast, none of the 3 histological factors tested were correlated with this response's intensity. CONCLUSION: Age, gender, and pre-therapeutic parietal invasion could be used to select "good" and "poor" responders to neo-adjuvant treatment in locally advanced rectal cancers.