Gastric cancer and associated pathogens: is there any association in Moroccan region?

Helicobacter pylori, Epstein-Barr virus and human papillomavirus are three pathogens associated with various human cancers. This study aimed to investigate the role of these pathogens in gastric cancer in Moroccan population. For this, a retrospective study has been conducted on participants attending the gastroenterology department of Hassan II University Hospital of Fez. A total of 279 participants were enrolled. H. pylori, EBV and HPV were detected and genotyped by PCR. In results, a significant association has been established between H. pylori, EBV and gastric cancer. 93.4% and 43.3% of gastric cancer cases are related to H. pylori and EBV respectively (p≤0.01). H. pylori-EBV co-infection is responsible of 31.6% of gastric cancer cases (p<0.01). Correlation between pathogens genotypes and gastric cancer shows 54.6% of GC EBV positives are carrying the 30 bp deletion in LMP1gene, while 16% of gastric cancers cases are carrying high-risk genotypes of HPV (p=0.21). The obtained results highlight the possible role of co-infection in gastric cancer development.

Uncommon Etiology of Pancreatic Mass: a Case Report.

IgG4-related autoimmune pancreatitis (AIP) is a chronic inflammatory disease of the pancreas with a distinct histological feature. Its diagnosis remains challenging as some features overlap with pancreatic cancer. We present a case of IgG4-related AIP mimicking pancreatic cancer. A 70-year-old male patient presented with epigastric pain, radiating to the entire abdomen with an unquantified weight loss. Magnetic resonance cholangiopancreatography (MRCP) showed a mass with a 28 mm long axis, in the head of the pancreas with pancreatic duct dilatation. Thus, it was presumed to be a pancreatic neoplasm and pancreatic resection was undertaken without a definitive preoperative diagnosis. In terms of clinical presentation, imaging characteristics, and laboratory parameters, IgG4-related AIP can resemble pancreatic cancer. Thus, histopathological studies remain the gold standard for a definitive diagnosis that may show a diffuse lymphoplasmacytic infiltrate with storiform fibrosis. On immunohistochemistry, the majority of plasma cells are positive for IgG4 (>50 per high-power field (HPF)). In our case, the histologic diagnosis allowed us to suggest the diagnosis of IgG4-related AIP and the immunohistochemical diagnosis confirmed the diagnosis. It is critical to distinguish pancreatic cancer from IgG4-related AIP due to its completely different prognosis and therapy. Steroids are the first-line treatment that allow a reduction of risk of relapse; therefore, a misdiagnosis as a malignancy leads to inappropriate surgical interventions. In this case, a biopsy is recommended.

Helicobacter pylori vacA allelic combination, dupA, cagE and cagA genotypes and their associations with gastric diseases among Moroccan population.

The combination of the four regions of vacA with cagA, cagE, dupA genes and cagA-EPIYA motifs, was studied to find the most likely combination that can be used as a disease determinant marker in Moroccan population. A total of 838 H. pylori positive obtained from consenting patients, that were previously analyzed by PCR to characterize vacA-s -m, -i regions, cagE status and cagA 3' region polymorphism, were used to characterize vacA-d region and to determine dupA gene status. The analysis shows the predominance of the less virulent combination (vacA(s2m2i2d2)dupA(-)cagE(-)cagA(-)), and shows that the risk of gastric cancer is 13.33 fold higher (1.06-166.37)) in patients infected by strains harboring vacA(s1m1i1d1)dupA(-)cagE(+)cagA(2EPIYA-C) compared to patients with gastritis without lesions and infected by H.pylori strains harboring vacA(s2m2i2d2)dupA(-)cagE(-)cagA(-). The infection with strains harboring vacA(s1m1i1d1)dupA(+)cagE(+)cagA(1EPIYAC) genotype combination represents a risk factor for gastric ulcer and duodenal ulcer (the Odds Ratio (95% CI) were 16 (1.09-234.24) and 6.54 (1.60-26.69) respectively) compared to patients with gastritis without lesions. These results suggest that the combination of the active form of vacA genotypes, dupA gene status and the number of EPIYA-C motif may be considered helpful markers to discriminate between several gastric diseases.

Basal cell carcinomas of the areola-nipple complex: Case report and review of the literature.

Basal cell carcinoma of the areola-nipple complex poses diagnostic and therapeutic challenges due to its rarity and unique anatomical location. This subtype of basal cell carcinoma necessitates meticulous management to address potential recurrence and metastasis. Surgical excision with clear margins remains the cornerstone treatment for basal cell carcinoma of the areola-nipple complex, while alternative modalities such as radiation therapy, Mohs surgery, and systemic therapies may be considered in specific cases. However, optimal management strategies remain contentious, with varying opinions on the necessity of aggressive surgical intervention to minimize recurrence and metastasis risks. Additionally, the absence of standardized diagnostic criteria and treatment guidelines complicates clinical decision-making. Herein, we present a rare case of basal cell carcinoma of the areola-nipple complex in a 47-year-old woman with a notable medical history of hypertension, type 2 diabetes, and untreated psychosis, alongside a family history of breast cancer in her aunt. The patient exhibited a non-regressing ulceration on the right areolar region of the breast, persisting for approximately 10 years and progressively extending over time. Following surgical excision, a favorable post-therapeutic course was observed during follow-up. This case underscores the diagnostic challenges and nuanced management considerations inherent in basal cell carcinoma of the areola-nipple complex, underscoring the imperative for tailored treatment approaches.

RAS Mutations Predict Recurrence-Free Survival and Recurrence Patterns in Colon Cancer: A Unicenter Study in Morocco.

PURPOSE: To date, only a few studies have investigated the role of molecular alterations in cancer recurrence. This exploratory study aimed to evaluate the impact of molecular alterations on the time and site of recurrence in patients with stage I-IV CRC and to identify the risk factors predicting recurrence-free survival in colon cancer. METHODS: A total of 270 patients were retrospectively included. We assessed the full RAS status using Sanger and pyrosequencing. MSI status was determined by immunohistochemical analysis. Molecular alterations were correlated with recurrence timing (early or late), recurrence patterns, and recurrence-free survival. Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. RESULTS: Of the 270 patients, 85 (31%) experienced recurrence, among whom 53% had mutant full RAS status, 48% had KRAS mutations, and 31.4% had KRAS p. G12V mutation subtype. Compared with those with late recurrence, patients with early recurrence were significantly older (P = 0.02) and more likely to have poorly differentiated tumors, a higher rate of positive lymph nodes, KRAS mutations, and especially KRAS p. G12V mutation variant. RAS mutation status, KRAS mutations, and rare mutations are more common in patients with lung cancer recurrence. Multivariate logistic regression analysis revealed that differentiation, perineural invasion, full RAS mutation status, and KRAS codon 13 mutations were independent factors for recurrence-free survival in colon cancer. CONCLUSION: In this cohort, the timing and patterns of recurrence appeared to be associated with the patient's molecular profile. KRAS codon 12 mutations were the worst predictors of recurrence-free survival at all stages in our population.

An inflammatory myofibroblastic tumor of the ampulla of Vater, an exceptional location: a case report.

Introduction and importance: Inflammatory myofibroblastic tumors constitute a group of mesenchymal tumors associated with inflammatory infiltration. They occur mainly in young patients. It is classified by the World Health Organization as a borderline neoplasm. They are observed in many organs, particularly the lungs. Digestive localization is rare, and localization into the ampulla of Vater has been reported once. Case presentation: We report the case of a 39-year-old patient who was admitted for cholestatic jaundice with right hypochondrium pain. Computed tomography and magnetic resonance imaging revealed a tumor at the biliopancreatic junction. A cephalic duodenopancreatectomy was performed, and a histological examination of the surgical specimen revealed an inflammatory myofibroblastic tumor of the ampulla of Vater. The postoperative evolution was without any complications. Clinical discussion: This is the second case of localization of an inflammatory myofibroblastic tumor in Vater's ampulla. The therapeutic approach is the complete excision of these inflammatory tumors, thus reducing the risk of local recurrence. In the literature, all cases of incomplete excision have resulted in recurrences. Conclusion: Inflammatory myofibroblastic tumors are rare. The diagnosis was based on histopathological findings and confirmed using immunohistochemical techniques.

Secretory Breast Carcinoma: Report of Two Cases and Literature Review.

Secretory Breast Carcinoma (SBC) is a rare subtype of breast cancer, predominantly affecting young women, and characterized by hormone receptor-negative and HER2-negative tumors with distinctive histological features, including secretory droplets within tumor cells. This article presents 2 unique cases of SBC, Case 1 involving a 42-year-old woman with triple-negative mammary carcinoma later diagnosed with triple-negative secretory carcinoma, and Case 2 featuring a 48-year-old woman with poorly differentiated adenocarcinoma subsequently identified as invasive mammary carcinoma of secretory type. Both cases received diverse treatment regimens, incorporating surgery, chemotherapy, radiotherapy, and hormone therapy. The importance of accurate diagnosis and the need for further research to optimize the management of this rare breast cancer subtype are emphasized. Raising awareness of SBC and reporting additional cases can enhance understanding and improve patient outcomes. Additionally, the integration of clinical, radiological, and histopathological findings, alongside specific molecular markers like S-100 and mammaglobin, is crucial for accurate SBC diagnosis. Given the lack of established guidelines for SBC management, collecting additional cases can aid in defining a more effective strategy for diagnosis, monitoring, and treatment, ultimately contributing to advancements in the field. Herein, we report 2 cases of this rare disease that were diagnosed and treated in our institution.

Histopathologic and Molecular Features of Cutaneous Melanoma in a Moroccan Population.

Background Cutaneous cancer is the most common malignancy type, among which melanomas are considered the most aggressive and lethal. In Morocco, skin melanoma is the 25th most common cancer. To our knowledge, this is the first and largest Moroccan study specifically describing cutaneous melanoma.  Materials and methods We obtained data for 100 patients diagnosed with cutaneous melanoma in the Department of Pathology of Hassan II University Hospital, Morocco. Clinical, histopathological, molecular, and follow-up data were recorded from pathology request forms and the patient's medical records.  Results The mean age of our patients was 65 years old. Histologically, the most prevalent were the nodular (48%) and acro-lentiginous (38%) melanoma subtypes. A total of 66% of the patients had a Breslow thickness of >4 mm. The presence of ulceration was noted in 46% of cases. The average mitoses was 9/1 mm². A total of 44% of patients had metastatic melanoma at the time of diagnosis. The BRAF V600E mutation was found in six cases, and the C-KIT mutation in five cases. The five-year overall survival and metastasis-free survival were 85% and 15%, respectively. There was a significant correlation between Breslow thickness and Clark's level (p<0.001), histologic subtype (p=0.012), and presence of metastasis (p=0.002). There was a significant difference between the head and neck melanomas and those of the feet, particularly in the histological subtype and the presence of ulceration. BRAF V600E mutation was found in six cases of metastatic melanomas of the head and neck, of which three cases were positive for this mutation, as compared with the 23 cases of acral melanomas, which tested negative for the same mutation.  Conclusion The results of our study showed that cutaneous melanomas were characterized by advanced age at diagnosis and late-stage diagnosis with a high Breslow index. The lower limbs were the most affected sites, especially in the plantar region. The acral lentiginous subtype was the most common. The presence of BRAF V600E mutation was associated with a better prognosis.

Moroccan Children With Helicobacter pylori Infection: Demographics, Clinical Features, and Histological Findings.

BACKGROUND: Infesting nearly half of the world's population, Helicobacter pylori is thought to cause peptic ulcers and gastric adenocarcinoma. Several studies have examined the association between H. pylori and socioeconomic, clinical, and histological factors in pediatric populations. Similarly, this study aimed to describe the characteristics of H. pylori infection in Moroccan children. METHODS: Patients aged 1-17 years who underwent upper gastrointestinal endoscopy over a period of two years from January 2019 to January 2021 were included in this study. Gastric biopsies from the antrum and corpus of the stomach were collected. Detection of H. pylori infection was confirmed by Giemsa stain. Demographic data and clinical and endoscopic characteristics were collected and histopathological findings with gastritis scoring were recorded according to the Sydney System. RESULTS: In 213 children, 95 (45%) were found to be infected with H. pylori, and the infection rates increased as the children aged. While no significant relationship between the infection of H. pylori and all symptoms was founded, a significant association was found in nodular gastritis (p<0.05), and 98% of the infected children had chronic inflammation, which was active in 22% and atrophic in 47%. The atrophy and activity were absent or mild, and the inflammation was mild to moderate. CONCLUSION: According to this study, nodular gastritis and nonspecific symptoms were related to H. pylori infection in Moroccan children. In addition, the association between this disease and gastric atrophy in our study needs the monitoring of the mucosa of Moroccan children with gastritis and identifying factors that may contribute to gastric cancer.

Prognostic Impact of Tumor Budding on Moroccan Gastric Cancer Patients.

Background: Tumor budding (TB) has been defined as an independent prognostic factor in many carcinomas like colon adenocarcinoma, but its prognostic impact on gastric cancer patients remains not well established. In the present study, we aimed to highlight the correlation of tumor budding with clinicopathological features and predict its survival outcomes in gastric cancer patients for the first time in the Moroccan population. Methods: This study was conducted on 83 patients who underwent surgery for gastric adenocarcinoma from 2014 to 2020. The patient's clinico-pathological characteristics were obtained from the pathological and clinical records of each patient. Tumor budding was assessed on HES slides, according to the 2016 International Tumor Budding Consensus Conference criteria. The association of tumor budding grades with categorical and continuous variables were respectively assessed by the χ2-test and the unpaired t-test. Survival analysis was performed by the Kaplan-Meier method, the log-rank test. Results: Patients consisted of 65.1% of men and 34.9% of women with a median age of 61.2 years. Histologically, the majority of the tumors were adenocarcinoma (65.1%). Among all cases, 18.1% were classified as Bud1 (15/83), (27/83) 32.5% as Bud 2, and 49.4% (41/83) as Bud 3 grades. High-grade tumor budding (BUD 3) was found to be significantly associated with special clinicopathological features including older age (P = .02), unradical resection (R1/R2) (P = .03), and the presence of vascular invasion (P = .05), and perineural invasion (P = .04). Furthermore, tumors with high-grade tumor budding were significantly associated with a low rate of resected lymph nodes (P = .04) and advanced TNM stage (P = .02). Among all stages, high-grade tumor budding was correlated with shorter overall survival in univariate and multivariate analysis (P = .04). Patients with high-tumor budding had worse relapse-free survival compared with patients with low-tumor budding grade (P = .01). Conclusion: According to our study, the high-tumor budding grade was correlated with unfavorable clinicopathological features and poorer survival. The present study findings suggest that tumor budding should be considered in the treatment and prognosis of gastric cancer patients.

Primary Cutaneous Malignant Perivascular Epithelioïd Cell Tumor (PEComa): Case Report With Review of the Literature.

Perivascular epithelioïd cell tumor (PEComa) is a mesenchymal neoplasm with epithelioïd or spindled morphology with numerous thin-walled capillaries between tumor cells. They co-express markers of both melanocytic and smooth muscle differentiation. PEComas are rare, presenting in numerous anatomic sites including lung, kidney, liver, genitourinary tract, soft tissue, and skin. Primary cutaneous PEComas are very rare entity, and malignant ones are even more uncommon. Herein, we report the case of a 92-year-old female which was presenting with 7 cm exophytic, ulcerated, hemorrhagic nodular tumor, and rapidly growing for 8 months over the right thigh. On histologic examination, we found a dermal neoplasm formed by an atypical clear cell tumor with numerous branching capillaries between tumor cells. The mitotic count was found 6 mitotic figures/10 HPF. On immunohistochemistry, tumor cells co-expressed smooth muscle and melanocytic markers, CD10, and CD68. Based on these findings, the diagnosis of primary cutaneous malignant perivascular epithelioïd cell tumor (PEComa) was made. The large size (7 cm), the count of mitoses (6 mitotic figures/10 HPF), and the nuclear pleomorphism argued for malignancy. The absence of soft tissue or visceral localization argued for the cutaneous primitive origin. Adjuvant radiotherapy and targeted therapy with mTOR inhibitor (nab-sirolimus) was indicated. To the best of our knowledge, this is only the eighth case of a primary cutaneous malignant PEComa reported in the literature to date.

Myoid Gonadal Stromal Tumor: A New Case Report with a Review of the Literature.

The myoid gonadal stromal tumor is a very rare testicular spindle cell tumor. Few cases have been reported in the literature from 1977 to 2022. It was an emerging entity in the fourth edition of the WHO Classification of Tumors of the Urinary System and Male Genital Organs and has been instated as a full benign entity in the new edition of 2022. We report herein an additional case of a myoid gonadal stromal tumor. It was a 27-year-old man who presented with an asymptomatic mass in his left testicle for 2 months. The mass was confirmed by ultrasound as a 3 cm solid well-circumscribed lesion for which orchiectomy has been performed. The histological analysis of the specimen and the immunohistochemistry staining was consistent with a myoid gonadal stromal tumor. The characteristics of this tumor are summarized in well-circumscribed, nonencapsulated masses of uniform spindle cells, and immunohistochemically, tumor cells coexpress SMA and S-100 protein. The benign behavior of this tumor is demonstrated by our results and those presented in the previous cases reported in the literature.

Malignant Melanocytic Matricoma: A Rare Skin Tumor That Can Clinically Mimic Melanoma.

Malignant melanocytic matricoma (MMM) is an extremely rare skin malignant neoplasm composed of epithelial cells with matrical differentiation and dendritic melanocytes. We found only 11 cases reported in the literature to date according to the databases consulted (PubMed/Medline, Scopus, and Web of Science). Here, we report a case of MMM in an 86-year-old woman. A histological examination showed a dermal tumor with a deep infiltrative pattern, without an epidermal connection. On immunohistochemical staining, tumor cells were positive for cytokeratin AE1/AE3, p63, and beta-catenin (nuclear and cytoplasmic staining) and negative for HMB45, Melan-A, S-100 protein, and androgen receptor. Melanic antibodies highlighted scattered dendritic melanocytes in tumor sheets. The findings did not support the diagnosis of melanoma, poorly differentiated sebaceous carcinoma, and basal cell carcinoma, but supported the diagnosis of MMM.

The high sensitivity and specificity of rapid urease test in diagnosis of Helicobacter pylori infection in Moroccan children.

Background and Objectives: Infesting nearly 50% of the world's population, Helicobacter pylori are thought to cause peptic ulcers, as well as gastric adenocarcinoma. Several diagnostic methods are available to detect this bacterium; however, at least two must be used together for an accurate diagnosis. This study evaluated the use of rapid urease test for diagnosis of H. pylori infection in a pediatric population. Materials and Methods: Five gastric biopsies were taken from children during a 2-year period for the purpose of histological, molecular, bacteriological culture, and rapid urease testing. Results: Among 83 children, 38 were male, and 45 were female with an age ranging of 2 to 15 years. The infected group represented 31%. The rapid urease test had a sensitivity of 88.5%, a negative predictive value of 94%, a specificity of 84.2%, and a positive predictive value of 72%. Conclusion: A rapid urease test may be appropriate for ruling out H. pylori infection after a negative result. The positive results however, may be confirmed by a second invasive test.

Lymph Nodes With Germinal Centers Are Not Associated With Tumor Response After Neoadjuvant Treatment in Locally Advanced Rectal Cancer.

In patients with locally advanced rectal cancer, neoadjuvant radiotherapy or chemoradiotherapy followed by total mesorectal excision as a standard of care. We aimed to explore the number, size, germinal centers, extracapsular invasion of lymph nodes (LN), and their impact on overall survival and disease free survival. Furthermore we also investigated the characteristics of lymph nodes in patients who received neoadjuvant therapy and those who underwent surgery between 2011 and 2018. The count and measurement of lymph nodes was assessed by careful visual inspection and manual palpation. The predictive cut-off value of the lymph node ratio (LNR) was determined based on the receiver operating characteristic (ROC), method and the survival outcomes based on Kaplan-Meier curves. We found that the size and the number of lymph nodes decreased significantly after neoadjuvant treatment. The mean LN for patients who received neoadjuvant therapy was 12.68 ± 6.69 and for patients who did not receive neoadjuvant therapy was 16.29 ± 5.61 (P = .012). The average size for patients who received neoadjuvant therapy followed by surgery was 3.30 ± 1.10 versus 4.22 ± 1.18 mm for control group (surgery only) (P < .001), an LNR of 0.13 (sensitivity: 86%, specificity: 47%, AUC: 60%, 95% CI, 0.41%-0.76%) predicted recurrence and metastasis. Presence of lymph nodes with germinal centers was significantly associated with absence of vascular invasion, nodal tumor deposits, distant metastasis, and lower age group (<50 years). However there was no association seen between overall survival and relapse free, total number of lymph nodes enlarged and extracapsular invasion in positive nodes. Finally there is no association between lymph nodes with germinal centers and tumor response after neoadjuvant treatment in locally advanced rectal cancer.

Molecular classification of soft tissue sarcomas for adequate diagnosis: A study on the northeast population of Morocco.

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors. For adequate therapeutic management, an accurate diagnosis is necessary. In Morocco, the diagnosis is essentially based on the morphological and immunohistochemical study. Compared to other techniques, fluorescence in situ hybridization (FISH) is easier to develop and less expensive. This study aims to assess the feasibility and utility of implementing FISH technique to improve diagnostic accuracy and establish a good classification. Material and methods: This is a retrospective cohort study. 211 cases of mesenchymal tumors were included. Hematoxylin Eosin Safran (HES) staining was performed in all cases followed by immunohistochemistry (IHC). FISH was performed in all cases with suspected STS. The probes used were EWSR1, MDM2 and SS18. The performance of FISH and histopathological test were evaluated by the ROC curve method (receiver operating characteristic). We evaluated the concordance between FISH and real time PCR by Cohen test. Results: The real-time PCR technique showed good agreement with the FISH test by a Kappa coefficient of 60% (p = 0.035). FISH was able to confirm that it is more accurate (Youden's Index = 91%) than histological/immunohistochemical analysis (Youden's Index = 51%), as well as the positive predictive value was higher (100%) with an ROC curve finding a larger area under the curve of 0.953 (95% CI: 0.918-0.988), p = 0.000 which supports that FISH shows high performance to present an accurate final diagnosis. Conclusion: This is the first and the largest Moroccan series for the molecular diagnosis of STS by FISH. Our study shows that paraffin FISH is a sensitive and specific ancillary tool in the diagnosis of STS when used in the appropriate clinicopathological context.

Dermatofibrosarcoma protuberans of the anterior abdominal wall: case report and literature review.

Dermatofibrosarcoma protuberans (DFSP) is a rare and slowly growing cutaneous tumor with high risk of local invasion and recurrence. Here, we report a case of a DFSP of the anterior abdominal wall diagnosed in a 45-year-old woman. The clinical examination showed an indurated well-limited oval mass localized in the supra-umbilical level and measuring 5 cm by 3 cm. The histological finding of skin biopsy was consistent with the diagnosis of DFSP. A wide local excision was performed while respecting minimum safety margins of 3 cm. The primary closure was possible after advancing the subcutaneous adjacent tissue. The histological examination of the surgical specimen confirmed the DFSP diagnosis and determined safe microscopic margins. After 4 years of regular follow-up, no locoregional or distant recurrence was observed. We discuss through this case the diagnosis difficulties and the particularities of the abdominal wall localization.

[Unusual localisation of rare primary skin carcinoma: a case report]. / Une localisation inhabituelle d'un carcinome primitif cutané rare: à propos d'un cas.

Adnexal carcinomas are rare, accounting for less than 1% of skin carcinomas. Sclerosus carcinoma of the sweat glands was first described by Goldstein et al. in 1982. We here report the case of a 33-year-old female patient with a retracted perianal skin lesion. Histological examination of perilesional skin biopsy, immunohistochemistry, and negative results of laboratory tests, radiological and endoscopic investigations allowed for the diagnosis of eccrine sclerosus carcinoma. This is a rare tumor, usually characterized by facial localization and slow but aggressive progression. It poses problems in differential diagnosis with benign and malignant tumors; hence the challenge encountered by pathologist of suspecting this carcinoma in patients with any sclerotic and infiltrating skin lesion characterized by slow progression, in a context of preservation of the general state and in the absence of neoplastic history as well as of feeling free to ask for new deep biopsies when in doubt.

Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients.

BACKGROUND: Tumor budding is now emerging as one of the robust and promising histological factors that play an important role in colon cancer. In this study, we aimed to investigate the association between tumor budding and tumor clinicopathological factors, tumor molecular signature, and patient survival for the first time in a Moroccan population. METHODS: We collected data of 100 patients operated from colon adenocarcinoma. Tumor budding was assessed on HES slides, according to the International Tumor Budding Consensus Conference 2016 recommendations. The expression of MMR proteins was performed by immunohistochemistry. KRAS and NRAS mutations testing was performed by Sanger sequencing and pyrosequencing. RESULTS: High tumor budding grade (BUD 3) was found to be significantly associated with adverse clinicopathological features including older age (P=0.03), presence of perineural invasion (P=0.02), presence of vascular invasion (P=0.05), distant metastases (P < 0.001), advanced TNM stage (P=0.001), the occurrence of relapse (P=0.04), and the high number of deceased cases (P=0.02). Interestingly, we found that tumors with high-grade tumor budding were more likely to be microsatellite stable (MSS) (P=0.005) and harbor more KRAS mutations (P=0.02). Tumors with high-grade tumor budding were strongly associated with KRAS G12D mutation (P=0.007). In all stages, high tumor budding was correlated with poorer overall survival (P=0.04) and decreased relapse-free survival with a difference close to significance ((P=0.09). We concluded that high tumor budding was strongly associated with unfavorable clinicopathological features and special molecular biomarkers and effectively affects the overall survival of CC patients. CONCLUSIONS: Based on these findings and the ITBCC group recommendations, tumor budding should be taken into account along with other clinicopathologic factors in the risk assessment of colorectal cancer.

Dietary Fat Intake and KRAS Mutations in Colorectal Cancer in a Moroccan Population.

Epidemiologic data support an association between diet and mutations in the Kirsten-ras (KRAS) gene involved in colorectal cancer (CRC) development. This study aimed to explore the associations between fat intake and KRAS mutations in codons 12 and 13 in cases of CRC in the Moroccan population. A multicenter case-series study nested in a large-scale Moroccan CRC case-control study was conducted. Among all CRC cases recruited, 151 specimens were available for the DNA mutation analysis. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cis) for KRAS mutation status according to the fat intake variables. A KRAS mutation was detected in the CRC tumor of 34.4% of the patients among whom 65.4% had a single mutation at codon 12 and 34.6% had a single mutation at codon 13. Compared to low levels of consumption, a positive association was observed between high polyunsaturated fatty acids (PUFA) consumption (>16.9 g/day) and prevalence of KRAS mutations (OR = 2.15, 95% CI = 1.01-4.59). No statistically significant associations were observed for total fat, monounsaturated fatty acids, saturated fatty acids and KRAS mutations. The results of this study suggest that PUFA may be relevant in the etiology of CRC, possibly through the generation of G > A transitions at the KRAS oncogene. Further studies are needed to verify and explain this finding.