Immunohistochemical predictors in squamous cell carcinoma of the tongue and floor of the mouth.

BACKGROUND: The purpose of this study was to evaluate the clinical usefulness of the immunoexpression of Ki-67, matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF)-C, and VEGF-D in predicting follow-up treatment in patients with squamous cell carcinoma (SCC) of the tongue and floor of the mouth (FOM). METHODS: Marker expression was evaluated in surgical specimens taken from 60 patients who underwent surgery because of primary SCC without prior therapy. RESULTS: Strong MMP-2 expression was positively correlated with a higher risk of nodal recurrence (p = .047). Strong VEGF-C expression was found in patients with distant metastases (p = .008). Cox's regression model showed high Ki-67, MMP-2, and VEGF-C expression, which were independent predictors of disease-specific survival (p = .001, p = .002, and p < .001, respectively). CONCLUSION: It seems that targeting MMP-2 and VEGF-C may improve local control, thereby reducing the risk of distant metastasis in patients with SCC of the tongue and FOM. © 2015 Wiley Periodicals, Inc. Head Neck 38: E747-E753, 2016.

Endolymphatic sac tumour (ELST). Case report of a rare tumour of the temporal bone, presenting as a mass in a cerebello-pontine angle.

Endolymphatic sac tumour (ELST) is a primary low-grade, locally invasive adenocarcinoma of the endolymphatic sac, characterized by the proliferation of cuboidal cells forming a papillotubular pattern and colloid-filled cysts. Rare in the general population, it coincides significantly with the presence of von Hippel-Lindau disease. The natural history, mechanisms underlying the early symptoms, anatomical origin of ELST and optimal timing of their treatment are unknown. In this study, we report a Polish male patient with sporadic ELST (without a family history of VHL disease) along with a review of literature. The light microscopic and immunohistochemical features as well as clinical presentation were typical of ELST.

HER-3 expression in HER-2-amplified breast carcinoma.

AIM OF THE STUDY: To determine whether the expression of HER-3 influences the survival of HER-2 positive patients with breast cancer (BC). MATERIAL AND METHODS: In the present work, the expression of HER-3 in a group of 35 HER-2 positive patients with BC was studied by performing immunohistochemistry (IHC) in formalin-fixed paraffin embedded tissues. RESULTS: Higher HER-3 status if estimated by IHC correlated significantly with older age of the patients. HER-3 expression did not correlate with estrogen or progesterone receptor status, pT or pN. There was also no significant difference in disease-free or overall survival (DFS and OS) between groups with different HER-3 expression, although some tendencies were seen as HER-3 expression in over 50% of cells was a factor of worse 5- and 10-year survival. CONCLUSIONS: Further studies should be performed on a larger group of patients to confirm the prognostic role of HER-3 status determined by IHC in BC.

[Neurothekeoma of the orbit]. / Przypadek neurothekeoma oczodolu.

AIM: The aim of this study was to present a rare benign tumour of neural origin located in the orbit. MATERIAL AND METHODS: Authors describe case of six-year-old boy with tumour of the right orbit, upper eyelid and right zygomatic fossa. Medical history revealed gradually increasing in size, painless tumour. Before admission to the hospital computed tomography was taken to assess the size, localization of the tumour and to plan the proper treatment. RESULTS: The patient was operated on using Krönlein approach. Tumour was removed in macroscopically radical limits without need to incise the muscles responsible for eye movement. Histopathological examination revealed: Neurothekeoma, classic type. During one year follow-up there was no recurrence. CONCLUSION: Neurothekeoma may occur in young boys in eyelid and orbit. A unique localization of neurothekeoma in the orbit, close to the lacrimal gland shows that this kind of histopatological tumours may infiltrate deeper tissues. Surgical treatment of neurothekeoma is the same as in other benign tumours.

Gene expression profiles in human ruptured and unruptured intracranial aneurysms: what is the role of inflammation?

BACKGROUND AND PURPOSE: Mechanisms underlying development and rupture of intracranial aneurysms (IA) are poorly recognized. The majority of studies on human tissue have focused on predefined pathways. We sought to analyze global gene expression patterns of ruptured IA, unruptured IA, and control vessels. METHODS: Transcription profiles were studied in human ruptured (n=8) and unruptured (n=6) IA, as well as in control intracranial arteries (n=5), using oligonucleotide microarrays. Real-time reverse-transcription polymerase chain reaction was used for confirmation. Functional analysis for determination of over-represented ontological groups among gene expression profiles was also performed. RESULTS: The expression of 159 genes differed among the studied groups. Compared to the controls, 131 genes showed common directions of change in both IA groups. The most impacted biological processes for IA are: (1) the muscle system; (2) cell adhesion (downregulation); and (3) the immune system and inflammatory response (upregulation). Ruptured and unruptured IA differed in genes involved in immune/inflammatory processes; expression was reduced in ruptured IA. CONCLUSIONS: Decreased expression of genes related to muscle system and cell adhesion is important for the development of IA. The role of immune/inflammatory processes is unclear. Inflammation may participate in the healing process within IA while playing a protective role against IA rupture.

CDH1 gene promoter hypermethylation in gastric cancer: relationship to Goseki grading, microsatellite instability status, and EBV invasion.

Hypermethylation of the CDH1 promoter region seems to be the most common epigenetic mechanism in this gene silencing in gastric cancer. In this study, CDH1 promoter hypermethylation was observed in 54.8% (46/84) of the analyzed sporadic gastric carcinomas. We introduce a new relation: clustering of Goseki grading into 3 grade was determined by CDH1 promoter hypermethylation. The percentage of methylation in Goseki III cancers was significantly higher (83%) when compared with other grades; the lowest proportion was detected in IV (36%) and II (38%) groups, whereas grade I demonstrated typical percentage of promoter hypermethylation. A novel polymorphism R732R in exon 14 of the CDH1 gene was detected by mutational analysis. Additionally, all cases with the MSI-high phenotype revealed CDH1 promoter hypermethylation. In MSI-low and MSS gastric cancers, this percentage was lower, reaching 71% and 41%, respectively. Moreover, the methylation status was correlated with the LOH phenotype. We detected CDH1 promoter hypermethylation in all EBV-positive gastric cancers (5/5), whereas methylation in the EBV-negative group occurred in 58% of cases. We also report that "methylated" tumors were slightly larger than "nonmethylated," whereas the second group revealed a higher probability of longer patient survival, though these relationships were not statistically significant. These results suggest that downregulation of E-cadherin, caused by promoter hypermethylation, in sporadic gastric carcinomas may be associated with a worse prognosis and specific tumor phenotype.

EBV-positive gastric carcinomas in Poland.

Epstein-Barr virus plays a substantial role in numerous human neoplasms including gastric carcinoma, as proved recently. In our series EBV has been detected in five cases of forty (12.5%) gastric carcinomas. It may indicate that Poland is one of the countries with the highest EBV-induced gastric carcinoma incidence worldwide.

ABL-kinase domain point mutation as a cause of imatinib (STI571) resistance in CML patient who progress to myeloid blast crisis.

Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mutations within ABL-kinase domains. A point mutation leading to substitution at the ATP binding site of ABL-kinase and insensitivity to imatinib was detected in our patient treated with imatinib, who progressed to blast crisis. Additionally, clonal evolution could lead to BCR-ABL-independent proliferation. Early detection of ABL-kinase mutation could predict the progression of CML treated with imatinib.

The comparison of the agreement in determining the histological grade of uterine endometrial endometrioid carcinoma, using the three-grade FIGO classification and the two-grade system.

The objective of the investigation was to compare the degree of interobserver agreement in determining the histological grade of uterine endometrial endometrioid adenocarcinoma using the criteria proposed by the three-grade FIGO classification (1988) and the new, two-grade system proposed by Lax et al. (2000). In the FIGO system, the assessment is focused on the amount of solid, non-squamous growth pattern and the additional feature is the presence of the so-called "notable nuclear atypia" (nuclear grade), with the latter criterion not having been precisely defined. In the two-grade system, the evaluation concentrates on the amount of the solid component, regardless of its character, type of neoplastic growth pattern (expansive or diffusely infiltrating) and the presence of necrosis within the tumor mass. A total of 133 cases of uterine endometrial carcinoma were evaluated, determining the stage according to the FIGO classification and assessing the histological grade based on the criteria presented by the above two systems. All the cases were separately examined by 5 pathologists with varying degrees of experience in gynecological pathology. A higher degree of interobserver agreement was demonstrated when the two-grade system was employed as compared to the FIGO system, regardless whether the material was evaluated by experienced pathologists (FIGO k - 0.64 - 0.71, binary - 0.91 - 0.92), or by individuals with little experience in gynecological pathology (FIGO k - 0.23 - 0.48, binary - 0.21 - 0.57). The data point to the superior character of the two-grade system as to the agreement of the histological grade assessment, but also suggest a considerable effect of experience on the precision of the evaluation.

Assessing microvessel density in gastric carcinoma: a comparison of three markers.

Angiogenesis (AG) is necessary for cancer progression. In some cases the intensity of AG may affect the prognosis. The aim of the study was to compare the results of vessel density assessment using the stereological method and immunohistochemical reactions for three endothelial markers: CD31, CD34 and vWf. The material consisted of 40 gastric carcinoma cases. The specimens were processed and the immunohistochemical reactions performed routinely. To assess the microvascular density the stereological parameter of "length density" and the "hot spots" method were employed. Image acquisition and the measurements were done using the image analysis system AnalySIS 3.0 pro with custom-made applications. It was observed that CD34-stained preparations were the easiest to assess. The number of labeled vessels, and especially microvessels, was also the highest in the case of the above reaction. The results achieved in AG evaluation using various endothelial markers are not directly comparable. The vascular network density was significantly associated with tumor stage. Such an association was most clearly seen in CD34 reactions.