BACKGROUND: Microsatellite instability (MSI) is the genetic pathway underlying 15% of sporadic colorectal carcinoma (CRC) and hereditary non-polyposis CRC. MSI-H CRC has a distinct clinicopathological characteristic including excess mucin and signet ring component, proximal colon, Crohn’s like reaction, lymphocytic infiltration, and better survival. AIM: This research aims to screen Egyptian CRC patients for MSI status by IHC testing of expression of the MMR proteins in correlation to its clinicopathological features. MATERIAL AND METHODS: Immunohistochemistry study for mismatch repair proteins (MMR) was done on 115 cases of CRC. Their expressions were assessed and correlated to clinicopathological parameters in an attempt to obtain the most significant predictors of MSI. RESULTS: MSI (low and high) represents 67% of the study cases. The most frequent expression pattern was combined loss of MLH, and PMS2 (38% of MSI) followed by a combined loss of MSH2, and MSH6 (29% of MSI). There was significant correlation of expression pattern of MMR proteins with the laterality, lymphovascular emboli, perineural invasion, grade, T stage, N stage, signet ring component, tumor infiltrating lymphocyte, and peritumoral lesion (0.014, 0.035, 0.012, 0.033, 0.013, 0.000, 0.041, 0.012, and 0.009 respectively). Proximal location (right sided) and lower grade, higher nodal stage, and marked TIL were selected as predictors of MS-H CRC (0.005, 0.031, 0.025, and 0.000 respectively). CONCLUSION: All clinicopathological and histological parameters should be assessed in CRC for the sake of predicting MSI. The optimal approach to MSI evaluation is (IHC) assessment of MMR proteins.

Background and objectives Accurate recognition of urinary bladder muscularis propria (MP) invasion by urothelial carcinoma is crucial as it is the critical crossroad between conservative and aggressive management for the patient. It is now widely known that an inconsistent layer of muscularis mucosae (MM) muscle exists in the lamina propria, which can mimic the MP muscle, particularly when hyperplastic, making staging extremely challenging in some limited, unoriented, or highly cauterized specimens.Smoothelin is a novel smooth muscle-specific contractile protein expressed only by fully differentiated smooth muscle cells, and not by proliferative or noncontractile smooth muscle cells and myofibroblasts. Materials and methodsWe performed immunohistochemical staining in the bladder for smoothelin to evaluate its expression in MM and MP muscle in 60 cystectomy specimens and by comparing the staining pattern with desmin.Results In contrast to desmin, which equitably stained both types of muscle fibers, smoothelin showed striking differential immunoreactivity between MM and MP muscle.Smoothelin was expressed in different intensities and showed different immunoreactivity between MM and MP muscles. The MM showed absent (44/60, 73%) or weak staining (15/60, 25%), only one showed moderately positive staining (1/60, 1.6%), and none showed strong staining (0/60, 0%). In contrast to the MM, the MP predominantly showed strong staining (36/60, 60%) and moderate staining (24/60, 40%), with none showing weak or negative staining (0/60, 0%). There was always a significant and striking disparity in the staining intensity between the MM and the MP in every section (in cases where smoothelin was weak in the MM, it was always stronger in the MP).Conclusion The relatively distinct immunohistochemical staining pattern of smoothelin between MP and MM (including its hyperplastic forms) makes it a robust and attractive marker to be incorporated into the contemporary diagnostic armamentarium for the sometimes difficult area of staging bladder urothelial carcinoma. It also confirmed the use of desmin to differentiate between smooth muscle cells (whether MM or MP) and proliferating myofibroblasts.

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Interstitial deletion of the long arm of chromosome 4 is rare. Patients with interstitial deletion of the long arm of chromosome 4 differ from those with terminal deletions. Phenotypes may be variable, depending upon the specific length and location of the deleted portion. Here, we report on a boy exhibiting most of the congenital malformations encountered in terminal 4q syndrome. The conventional karyotyping and Fluorescence in-situ hybridization revealed a de novo interstitial del (4)(q31q32). The current report is a further document highlighting that deletion of segment q31 could be contributing to the expression of most of the phenotype of 4q deletion syndrome. Using array comparative genome hybridization methodology is recommended for investigating further cases with similar segmental interstitial deletions to support and delineate findings and to define genes implicated in the pathogenesis of the disorder.

Background Wolf–Hirschhorn syndrome (WHS) (OMIM 194190) is a multiple congenital anomalies/intellectual disability syndrome. It is caused by partial loss of genetic material from the distal portion of the short arm of chromosome. Methods We studied the phenotype–genotype correlation. Results We present the clinical manifestations and cytogenetic results of 10 unrelated Egyptian patients with 4p deletions. Karyotyping, FISH and MLPA was performed for screening for microdeletion syndromes. Array CGH was done for two patients. All patients exhibited the cardinal clinical manifestation of WHS. FISH proved deletion of the specific WHS locus in all patients. MLPA detected microdeletion of the specific locus in two patients with normal karyotypes, while array CGH, performed for two patients, has delineated the extent of the deleted segments and the involved genes. LETM1, the main candidate gene for the seizure phenotype, was found deleted in the two patients tested by array CGH; nevertheless, one of them did not manifest seizures. The study emphasized the previous. Conclusion WHS is a contiguous gene syndrome resulting from hemizygosity of the terminal 2 Mb of 4p16.3 region. The Branchial fistula, detected in one of our patients is a new finding that, to our knowledge, was not reported.

BackgroundMicrodeletion of 1q43q44 causes a syndrome characterized by intellectual disability (ID), speech delay, seizures, microcephaly (MIC), corpus callosum abnormalities (CCA) and characteristic facial features. Duplication of 4q is presented with minor to severe ID, MIC and facial dysmorphism. We aimed to verify the correlation between genotype/phenotype in a patient with 1q43q44 deletion associated with 4q32.1q35.2 duplication.Case presentationWe report on a 3 year-old female patient with delayed motor and mental milestones, MIC and facial dysmorphism. She is a child of non-consanguineous parents and no similarly affected family members. CT brain showed abnormal gyral patterns, hypogenesis of corpus callosum and bilateral deep Sylvian fissure. Electroencephalogram showed frontotemporal epileptogenic focus. Her karyotype was revealed as 46,XX,add(1)(q44). Fluorescence in situ hybridization (FISH) using whole chromosome paint (WCP1) and subtelomere 1q revealed that the add segment was not derived from chromosome 1 and there was the deletion of subtelomere 1q. Multiple ligation probe amplification (MLPA) subtelomere kit revealed the deletion of 1q and duplication of 4q. Array CGH demonstrated the 6.5 Mb deletion of 1q and 31 Mb duplication of chromosome 4q.ConclusionThe phenotype of our patient mainly reflects the effects of haploinsufficiency of AKT3, HNRNPU, ZBTB18 genes associated with duplication of GLRA3, GMP6A, HAND2 genes. Patients presented with ID, seizures, MIC together with CCA are candidates for prediction of 1q43q44 microdeletion and cytogenomic analysis.

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