IL-1RN +2018T>C polymorphism is correlated with colorectal cancer.

Epidemiological and experimental evidence indicates chronic inflammation as a risk factor for colorectal cancer. We investigated whether IL-1B -511C>T (rs16944), IL-1B +3954C>T (rs1143634) and IL1-RN +2018T>C (rs419598) cytokine polymorphisms are correlated with colorectal cancer. Blood samples were obtained from 377 Romanian subjects: 144 patients with sporadic colorectal cancer and 233 healthy controls. Polymorphisms were analyzed by allelic discrimination TaqMan PCR assays with specific probes. The results of our study showed that IL-1RN +2018T>C polymorphism is associated with colorectal cancer. We found that there was a significant difference in the frequency of CC genotype between patients with colorectal cancer and the control group (OR 2.42, 95 % CI: 1.06-5.53, p = 0,034) when TT genotype was used as reference. Furthermore, in a stratified analysis, a positive association was found only for IL-1RN +2018CC genotype, that was limited to early I and II stages (OR 2.72, 95 % CI: 1.05-7.03, p = 0,033). We did not find any association between any of the IL-1B polymorphisms and colorectal cancer. In conclusion this study found that IL-1RN +2018T>C polymorphism is associated with colorectal cancer, mainly for localized disease.

Cytokine promoter polymorphisms and risk of colorectal cancer.

BACKGROUND: Cytokines and chemokines are involved in cancer development and progression, but their role in colorectal tumorigenesis is still far from well defined. This study investigated the association between five cytokine promoter polymorphisms and risk, stage, and histological grade of colorectal cancer (CRC) in a hospital-based case-control study. METHODS: A total of 377 Romanian subjects were included in this study: 144 patients with sporadic colorectal cancer and 233 controls. Cytokine polymorphisms (IL-1B -31T > C, IL-4R -3223C > T, IL-8 -251T > A, IL-10 -1082A > G, and TNF-A -308G > A) were genotyped by allelic discrimination TaqMan PCR assay with specific probes. RESULTS: A significant association was observed for IL-10 -1082A > G polymorphism, the subjects carrying AG genotype were at a lower risk for CRC (OR 0.63, 95% CI: 0.40 - 0.98) when compared with the more frequent AA genotype. Furthermore, in a dominant model the carriers of G allele were protected against CRC (OR 0.64, 95% CI: 0.42 - 0.97). In a stratified analysis the only association between CRC and cytokine polymorphisms was found for carriers of IL-10 -1082G allele and was restricted to poorly differentiated cases (OR 0.36, 95% CI: 0.16 - 0.81). No association was observed for the remaining polymorphisms and CRC risk. CONCLUSIONS: This study shows that IL-10 -1082A > G polymorphism may influence CRC risk, the carriers of G allele being protected against CRC in the Romanian population.

Immunohistochemical evaluation of tumor budding in colorectal cancer: an important parameter with prognostic value.

We analyzed 82 patients with colorectal cancer (CRC) [75 patients with mucinous adenocarcinoma (ADK) and seven patients with "signet ring cell" ADK] using multi-cytokeratin (CK) AE1∕AE3 immunohistochemical assay. In order to determine the mucinous nature of some of the lymph node metastases of the mucinous colorectal ADKs studied, Periodic Acid Schiff-Alcian Blue (PAS-AB) histochemical staining was used. The counting results were systematized in the following ranges: 0 budding areas; between 1-4 budding areas; between 5-9 budding areas; and =10 tumor budding (TB) areas. The statistical analysis was performed using the Student's t-test. More than half of the cases of mucinous ADK revealed an increased intensity of TB, whereas in the case of "signet ring cell" ADK, an average intensity of this phenomenon. Mucinous ADKs, which were pT3 staged, showed an increased intensity of TB, and those in pT2 stage demonstrated, in the vast majority of cases, the absence of TB. There was a predominance of TB intensity in the absence of vascular-lymphatic invasion. Our study shows the existence of a concordance between tumor progression, the histological type of CRC, vascular-lymphatic invasion and the phenomenon of TB.

An unusual cause of acute surgical abdomen: benign multicystic peritoneal mesothelioma associated with adenomatous tumor.

Benign multicystic peritoneal mesothelioma (BMPM) is a rare disease that primarily affects fertile women with previous abdominal surgery. BMPM associated with adenomatous tumor is a single case report, according to our opinion. The patient had a history of abdominal surgery nine years ago for ovarian cysts. Upon admission, the diagnosis was acute surgical abdomen with acute peritonitis signs. The treatment applied consisted in the removal of peritoneal cysts and partial omentectomy. Only immunohistochemical examination established the diagnosis. The aim is to discuss diagnostic and therapeutic difficulties, underlining that there is no consensus on the use of chemotherapeutics. In conclusion, establishing a preoperative diagnosis is difficult if not impossible. One of the causes of acute surgical abdomen may be BMPM. The malignant transformation of this disease is rare, but the disease recurrence rate is over 50%, and it is often recommended to be monitored through abdominal computed tomography.

The influence of irradiation on autophagy process in normal and malignant colorectal epithelia.

AIM: The authors assessed the influence of preoperative radiotherapy on autophagy process using a quantitative assessment of LC3 expression on both normal and tumoral colorectal tissues. MATERIALS AND METHODS: Normal and malignant tissue samples were taken from 50 patients that underwent surgery for colorectal adenocarcinoma of which 11 received preoperative radiotherapy. Tissue samples were included in paraffin and sections were immunomarked for LC3 expression. LC3 percentage was assessed with dedicated software on 10 randomly selected fields with 40× objective from both normal and malignant tissue samples of each patient. The resulting data were assessed and compared with a statistical apparatus. RESULTS: LC3 was overexpressed in tumoral tissue as compared with normal one. The LC3 percentage is different from person to person and the higher it is in normal epithelium, the higher will be in tumoral epithelium of the same person, regardless the irradiation. The LC3 expression levels are decreasing from tumoral non-irradiated epithelia to normal irradiated epithelia. LC3 expression in tumoral cells is granular, with particular perinuclear disposal and often "annular" pattern. CONCLUSIONS: The autophagy process has a basal level in the normal tissue, with interindividual variability. The autophagy process proved to be upregulated in the tumoral cells, with a particular morphological expression, namely the presence of cytoplasmic coarse granules disposed in an "annular" pattern. Preoperative radiotherapy is downregulating the autophagy process both in normal and tumoral tissue but to a lesser extent in the latter.

Pyoderma vegetans of the posterior area of the neck: case presentation.

Pyoderma vegetans is a rare disease characterized by the presence of vegetant exudative, pustular and erythematous vesiculobullous plaque usually located in the inguinal area and axillary fold. Etiology of pyoderma vegetans is unknown but it is often associated with bacterial infections in immunocompromised patients. Main histopathological characteristics of pyoderma crops are pseudoepitheliomatous hyperplasia and subepidermal, intraepidermal neutrophilic or eosinophilic microabscesses. It is well known that these lesions are commonly associated with colonic inflammatory disease such as ulcerative colitis and Crohn's disease. Not available standard treatment for pyoderma vegetans, although the use of antibiotic therapy was often used with variable results. Standard first-line therapy is the systemic steroids yet. We perform excision of the lesion of the posterior area of the neck with application of the free split-thickness skin graft after 48 hours postoperatively. In this paper, we present a case of pyoderma vegetans with unusual location without associating colonic lesions and a review of literature related to therapeutic and diagnostic problems of this disease.

Retroperitoneal ancient schwannoma - case presentation.

Retroperitoneal ancient schwannomas are rare tumors, more usually found in the head, neck and flexor surfaces of the extremities. Ancient schwannomas are a subtype of classic schwannomas with a predominance of degenerative changes, calcifications, hemosiderin deposition, interstitial fibrosis and vascular hyaline degeneration. A 33-year-old male was referred on our hospital with a painful mass in left iliac fossa. The patient underwent surgery and intra-operatively the cystic encapsulated mass was found to be retroperitoneal, between the left psoas major muscle and left iliac muscle. On microscopic examination, we found the presence of Schwann cells in regions with high and low cellularity (Antoni A and B areas) and S100 protein immunohistochemical examination was intensely positive, being consistent with the diagnosis of schwannoma. Complete excision is the only method of the surgical treatment; schwannomas are not sensitive to radiotherapy and chemotherapy. Some authors consider that a complete excision of the tumor, while others believe that enucleated or partial excision of the tumor is sufficient. The prognosis is good, and the most common complication is recurrence, possibly by incomplete excision of it being reported in 5-10% of cases. In conclusion, retroperitoneal schwannomas is usually identified incidentally on tomographic images. Diagnosis is based on histopathological examination after surgery and immunohistochemical examination.

Preliminary study of correlations between the intratumoral microvessel density and the morphological profile of colorectal carcinoma.

AIM: New blood vessel formation (angiogenesis) is a fundamental event in the process of tumor growth and metastatic dissemination. The aim was to evaluate intratumoral vascular density (ITMVD) and to analyze possible correlations between ITMVD and the morphological profile of colorectal carcinoma. MATERIALS AND METHODS: The studied group consisted of 50 patients that underwent surgery for colorectal tumors, 12 of them receiving preoperatory radiotherapy. The analyzed morphological parameters were tumor site, tumor gross aspect, tumor longitudinal and transverse diameter, tumor grading, local invasion (pT), regional invasion (pN), distant metastases (pM) and intratumoral microvessel density (ITMVD) expressed as number of capillaries÷mm². The malignant tissue samples were included in paraffin blocks and serial tissue sections were cut both for Hematoxylin-Eosin staining and CD34 immunomarking. For each case, five consecutive fields without necrosis were randomly selected with ×10 objective. Quantitative measurements were performed using special software for image analysis. RESULTS: For non-irradiated colorectal tumors, ITMVD was the highest in rectal localization, in infiltrative tumors, in circumferential tumors, in tumors with low longitudinal extension, in moderately differentiated (G2) tumors and in pT4, pN0 and pM1 tumors. DISCUSSION: Correlations showed different trends of ITMVD depending on each parameter: ITMVD was higher when the tumor was closer to the rectum, when it was more infiltrative, more circumferential or with low longitudinal diameter. These trends might be exploited in defining future anti-angiogenic therapeutic strategies. CONCLUSIONS: There were some interesting correlations between ITMVD and studied morphological parameters that have to be validated on larger series of cases.

Determination of autophagy gene ATG16L1 polymorphism in human colorectal cancer.

Autophagy has emerged not only as an essential repair mechanism to degrade damaged organelles and proteins but also as a major player in protection of tumor cells from multiple stresses. It was shown that autophagy gene polymorphisms are correlated with development of chronic inflammatory lesions, which represent a risk factor for colorectal tumors. In this study, we aimed to determine if ATG16L1 +898A>G (Thr300Ala) polymorphism is associated with an increased risk of developing colorectal cancer (CRC) and to establish correlations between ATG16L1 genotypes and the major clinical and morphological parameters. We observed that subjects carrying GG genotype were at a higher risk for CRC (OR 1.99, 95% CI: 1.02-3.91, p=0.039) when compared with the more frequent AA genotype, furthermore this was even more consistent in male subjects (OR 2.72, 95% CI: 1.11-6.63, p=0.019) but not in female subjects (OR 1.29, 95% CI: 0.43-3.86, p=0.652). In addition, we noticed a correlation between ATG16L1 GG genotype and tumor stage in moderately and poorly differentiated CRC cases. GG genotype carrying patients were at a higher risk for CRC (OR 5.19, 95% CI: 1.50-17.87, p=0.002) when compared with the more frequent AA genotype. Such correlation suggests a possible role of autophagy gene polymorphisms in the development of human colorectal cancer.

MMR gene expression pattern in sporadic colorectal cancer.

BACKGROUND AND AIMS: Colorectal carcinoma is the second leading cause of death by cancer in Europe as its incidence increases with life span. Continuing research to detect new highly sensitive and specific noninvasive biomarkers is essential. The aim of this study was to compare 9 mismatching repair (MMR) genes activation levels in normal, polyp and malignant tissues in order to detect a MMR gene expression pattern in sporadic colorectal malignant pathology. METHODS: MMR mRNA levels were evaluated in tumor-normal tissue paired samples and polyps collected from 29 patients undergoing standard surgical procedures with curative intention. Real-Time quantitative Reverse Transcription PCR (qRT PCR) with TaqMan probes specific to ANKRD17, EXO1, MLH1, MLH3, MSH2, MSH3, MSH4, MSH5, MSH6 gene transcripts were used. RESULTS: The general tendency observed was a lower mRNA level of MMR genes in tumor samples compared with the normal tissue, with the exception of EXO1 gene. The number of patients that showed a higher expression of MMR genes in normal tissue was significantly greater than the number of patients that showed a higher expression inside the tumor (p=0.0024). ANKRD17 mRNA levels were higher in normal tissue than in tumor for 16 cases, by contrast with only 6 cases of higher mRNA levels in tumor. CONCLUSIONS: ANKRD17 mRNA appears to be the most sensitive target and may have a potential value as an additional marker for the existing multitarget assay panel for colorectal cancer detection.