Relationship of Histopathologic Parameters and Gene Expression Profiling in Malignant Melanoma.

BACKGROUND: Histopathologic characteristics (HC) are a mainstay in melanoma prognosis; gene expression profiling (GEP) has emerged as a potential additional independent value. OBJECTIVE: To elucidate HC predictive of groups obtained via GEP of malignant melanoma. METHODS: A retrospective study analyzing HC of 265 melanomas submitted for GEP over the course of 8 years. GEP was conducted as a part of regular clinicopathologic workup through Castle Biosciences Decision Dx®. RESULTS: Of the 265 cases, the major HC found to have an association with reported gene expression profiles were melanoma histology subtype, depth of invasion, and presence of ulcer. LIMITATIONS: This study is limited by its cross-sectional nature. Causation and long-term related outcomes of the use of GEP versus American Joint Committee on Cancer histopathologic staging cannot be ascertained by this design. CONCLUSIONS: An association, but no definitive prediction, exists between histopathologic categories of depth of invasion, melanoma subtype, and presence or absence of ulcer and gene expression profiles. GEP adds valuable data to the evaluation of malignant melanomas that cannot be definitively predicted by conventional models. The findings add to needed groundwork for comparison of traditional markers and molecular genotyping and begins to build a robust predictive model for better outcomes in patients with malignant melanoma.

Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer.

CDX2 expression loss is commonly associated with mismatch repair deficiency (dMMR) in colorectal cancer (CRC). However, there are only a few studies that have attempted to correlate CDX2 expression loss with specific MMR genes (MLH1, MSH2, MSH6, PMS2). This is a retrospective study of 327 patients who underwent surgery due to CRC. Nine patients (2.9%) had two synchronous CRCs, making the total sample 336 CRC. Histopathological data such as tumor type, tumor grade, perineural, lymphatic, and vascular invasion, pT stage, pN stage, peritumoral and intratumoral lymphocytic infiltration were collected and recorded in the database. After immunohistochemical analysis, CDX2 expression, MLH1, MSH2, MSH6, and PMS2 deficiency were also recorded. CDX2 expression loss was detected in 19 out of 336 CRCs (5.9%) and was associated with ascending colon CRC, partially mucinous adenocarcinoma, poorly differentiated carcinoma, and dMMR. Forty-four (13.1%) of CRCs were dMMR. We found a statistically significant association between CDX2 expression loss and MLH1 and PMS2 deficiency. Considering that most expression phenotypes include pairs of MMR genes, we analyzed MLH1/PMS2 and MSH2/MSH6 as heterodimers. Analysis of heterodimers showed a similar result, namely, that MLH1/PMS2 heterodimer deficiency was significantly associated with CDX2 expression loss. We also constructed a regression model for CDX2 expression loss and for dMMR. Poor tumor differentiation and MLH1/PMS2 heterodimer deficiency have been identified as potential predictors for CDX2 expression loss. CRC in the ascending colon and CDX2 expression loss have been identified as positive potential predictors of dMMR with rectal cancer as negative potential predictor of dMMR. Our study showed a significant association between CDX2 expression loss and MLH1 and PMS2 deficiency in CRC. We also managed to produce a regression model for CDX2 expression and showed that poor tumor differentiation and MLH1/PMS2 heterodimer deficiency are independent factors for CDX2 expression loss. We were the first to include CDX2 expression in a regression model for dMMR and showed that CDX2 expression loss can be used as a predictive factor for dMMR, which should be confirmed by further studies.

The Effect of Single and Triple Testicular Biopsy Using Biopty Gun on Spermatogenesis in Pubertal Rats.

BACKGROUND: The aim of this study was to compare consequences in single and triple testicular biopsy by biopty gun in pubertal rats using histological and immunohistochemical analysis. METHODS: Thirty-two Sprague-Dawley male rats were used as the experimental model. The rats were randomly divided into three study groups. The rats from the first group (n = 12) received a single-biopsy of upper pole of the left testis, while the rats from the second group (n = 10) received triple-biopsy of upper and lower poles and lateral surface of left testis. The third group (n = 10) was a control group. On the eightieth day after the biopsy in all rats bilateral orchiectomy and funiculectomy were performed to obtain testicular tissue and sperm for analysis. The consequences of the puncture were observed by pathohistology, immunohistochemistry and semen analysis. RESULTS: The results of the study showed lower percentage of sperm count (14.5 mill/mL vs. 16 mill/mL, p = 0.130), sperm motility (24.6% vs. 32.7%, p > 0.05), abnormal sperm (30% vs. 27%, p > 0.05), atrophic tubules (21% vs. 6%, p < 0.001), volume (1.7 mL vs. 2.28 mL, p < 0.01) and apoptotic index (1.56 vs. 1.19, p = 0.650) in the testes with a triple-biopsy compared to the testes with a single-biopsy. Semen analysis showed a borderline significant difference between the group with triple-biopsy where sperm count was lower than it in the control group (14.5 mill/mL vs. 17.5 mill/mL, p = 0.05). A single-biopsy has little effect on the testis, especially on overall fertility. A triple-biopsy showed higher degree of the testicular damage but without a significant impact on overall fertility. Semen analysis showed that single- and triple-biopsies did not have a significant effect on sperm count, motility and morphology. CONCLUSION: Biopty gun procedure is a cheap, simple and reliable method for testicular biopsy in rats without a significant effect on sperm count, motility and morphology.

Angiodysplasia of the Gallbladder: An Unknown Risk Factor for Cholecystolithiasis.

Angiodysplasia is a common type of lesion characterized by malformed submucosal and mucosal blood vessels. Angiodysplasia of the gallbladder is extremely rare, usually an incidental finding, with only two cases reported. Laparoscopic cholecystectomy is a curative treatment for angiodysplasia of the gallbladder. Our report describes a case of angiodysplasia of the gallbladder in a patient who underwent elective laparoscopic cholecystectomy for biliary colic because of gallstones, and a systematic literature review. We surmise that angiodysplasia of the gallbladder could be a risk factor for gallstones in younger female patients.

Superoxide dismutases in chronic gastritis.

Human gastric diseases have shown significant changes in the activity and expression of superoxide dismutase (SOD) isoforms. The aim of this study was to detect Mn-SOD activity and expression in the tissue of gastric mucosa, primarily in chronic gastritis (immunohistochemical Helicobacter pylori-negative gastritis, without other pathohistological changes) and to evaluate their possible connection with pathohistological diagnosis. We examined 51 consecutive outpatients undergoing endoscopy for upper gastrointestinal symptoms. Patients were classified based on their histopathological examinations and divided into three groups: 51 patients (archive samples between 2004-2009) with chronic immunohistochemical Helicobacter pylori-negative gastritis (mononuclear cells infiltration were graded as absent, moderate, severe) divided into three groups. Severity of gastritis was graded according to the updated Sydney system. Gastric tissue samples were used to determine the expression of Mn-SOD with anti-Mn-SOD Ab immunohistochemically. The Mn-SOD expression was more frequently present in specimens with severe and moderate inflammation of gastric mucosa than in those with normal mucosa. In patients with normal histological finding, positive immunoreactivity of Mn-SOD was not found. Our results determine the changes in Mn-SOD expression occurring in the normal gastric mucosa that had undergone changes in the intensity of chronic inflammatory infiltrates in the lamina propria.