FGFR-2 and Epithelial-Mesenchymal Transition in Endometrial Cancer.

BACKGROUND: At present, EC staging is based on the WHO conservative criteria, which only consider the percentage of gland formation. The molecular subgrouping of EC recently proposed by the Cancer Genome Atlas (TCGA) represents a milestone in precise molecular-based patient triage. The present study aimed to investigate the influence of FGFR-2 on the epithelial-mesenchymal transition (EMT) and whether it can lead to endometrial cancer dedifferentiation. METHODS: One hundred and three White female patients with confirmed EC were enrolled in our research. For the analysis, we performed next-generation sequencing and immunohistochemical analyses of E-cadherin, ß-catenin, and vimentin. RESULTS: Tumor grade progression was closely correlated with LVI (p = 0.0338), expression of vimentin (p = 0.000), tumor budding (p = 0.000), and lack of E-cadherin (p = 0.0028). Similar observations were noted with regard to TNM/FIGO stage progression. In terms of FGFR-2 mutation, we found the following correlation p-values: LVI (p = 0.069), expression of vimentin (p = 0.000), tumor budding (p = 0.000), and lack of E-cadherin (p = 0.000), RFS (p = 0.032), ECSS (p = 0.047). CONCLUSIONS: FGFR-2 is the important factor influencing on EMT.

Endometrial Cancer in Aspect of Forkhead Box Protein Contribution.

(1) Background: The present study aimed to investigate the influence of forkhead box (FOX) on endometrial cancer (EC) progression. For a better understanding, the driving mechanisms are vital to identifying correlations between genes and their regulators. (2) Methods: The study enrolled one hundred and three white female patients with confirmed EC. For the analysis, we used next-generation sequencing with the Hot Spot Cancer Panel provided by Illumina Inc., San Diego, CA, USA, and an immunohistochemical analysis of FOXA1, FOXP1, and estrogen receptors. (3) Results: FOXA1 silencing led to a worse outcome based on the correlation with FOXA1 (test log-rank p = 0.04220 and HR 2.66, p = 0.033). Moreover, FOX proteins were closely correlated with TP53 and KRAS mutation. (4) Conclusions: Our study confirmed previous reports about FOX box protein in the regulation of tumor growth. A remarkable observation about the unclear crosstalk with crucial genes, as TP53 and KRAS need deeper investigation.

The Roles of TP53 and FGFR2 in Progress Made Treating Endometrial Cancer.

The morbidity and mortality caused by endometrial cancer (EC) is still rising worldwide. In recent years, a new system of tumor stratification has been proposed based on POLE-mutational status, TP53, and microsatellite stability status. The aim of the study was to analyze a vast panel on the genes potentially involved in the genesis of endometrial cancer in the Polish population. One hundred and three white female patients with confirmed endometrial cancer were enrolled on the study. We performed sequencing using the Hot Spot Illumina panel and microsatellite stability with immunohistochemistry. We confirmed a key role of the TP53 mutation in progress to high-grade EC and parallelly some role of FGFR2 mutation. Moreover, our data present a vast landscape of mutations in EC and their polymorphism. We reported the meaning of FGFR2 mutation and TP53 (high copy number) in high-grade ECs. Our observation in MSI contribution is comparable with other studies. Finally, we see a strong need for the implementation of the TCGA classification.

Tumor Digital Masking Allows Precise Patient Triaging: A Study Based on Ki-67 Scoring in Gastrointestinal Stromal Tumors.

BACKGROUND: Technological advances constantly provide cutting-edge tools that enhance the progress of diagnostic capabilities. Gastrointestinal stromal tumors belong to a family of mesenchymal tumors where patient triaging is still based on traditional criteria such as mitotic count, tumor size, and tumor location. Limitations of the human eye and randomness in choice of area for mitotic figure counting compel us to seek more objective solutions such as digital image analysis. Presently, the labelling of proliferative activity is becoming a routine task amidst many cancers. The purpose of the present study was to compare the traditional method of prediction based on mitotic ratio with digital image analysis of cell cycle-dependent proteins. METHODS: Fifty-seven eligible cases were enrolled. Furthermore, a digital analysis of previously performed whole tissue section immunohistochemical assays was executed. Digital labelling covered both hotspots and not-hotspots equally. RESULTS: We noted a significant diversity of proliferative activities, and consequently, the results pointed to 6.5% of Ki-67, counted in hotspots, as the optimal cut-off for low-high-grade GIST. ROC analysis (AUC = 0.913; 95% CI: 0.828-0.997, p < 0.00001) and odds ratio (OR = 40.0, 95% CI: 6.7-237.3, p < 0.0001) pointed to Ki-67 16% as the cut-off for very high-grade (groups 5-6) cases. With help of a tumor digital map, we revealed possible errors resulting from a wrong choice of field for analysis. We confirmed that Ki-67 scores are in line with the level of intracellular metabolism that could be used as the additional biomarker. CONCLUSIONS: Tumor digital masking is very promising solution for repeatable and objective labelling. Software adjustments of nuclear shape, outlines, size, etc. are helpful to omit other Ki-67-positive cells especially small lymphocytes. Our results pointed to Ki-67 as a good biomarker in GIST, but concurrently, we noted significant differences in used digital approaches which could lead to unequivocal results.

Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability.

INTRODUCTION: Colorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the pathways driving to adenomagenesis is no less important. GOALS: Our purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also ß-catenin, BRAFV600E and p53 contribution. MATERIAL AND METHODS: The cohort included 101 cases of typical colon adenomas with high grade epithelial dysplasia according to WHO. An immunohistochemistry method was used for the depiction of the expression of targeted proteins, as also their heterogeneity. RESULTS: Generally, we noted a 10% frequency of MSI events where MSI-H reached a 5% share occurred within the left colon and rectal polyps. ß-catenin nuclear overexpression was noted with a 70% frequency and p53 with close to a 24% frequency. In addition, we found a presence of micro-serration foci more often within tubular adenomas, where focal MSI took place more often. Our results indicate that MSI events occur more often than had been theorized earlier. It results in tumour heterogeneity, more complex underlying pathways and finally ontogenetic molecular-diversity of tumours besides similar occurring histopathological features.

CD63 and GLUT-1 Overexpression Could Predict a Poor Clinical Outcome in GIST: A Study of 54 Cases with Follow-Up.

Background and Goals. In light of current knowledge, it seems that alternations underlying GISTs are well explained, although all that is enhanced by various aspects on a daily basis. More recently, attention has been pointed towards exosomes as important particles able to modify healthy and also diseased tissues including cancer. The goal of the present study was an analysis of CD9, CD63, and GLUT-1 as a marker of hypoxia status within 54 cases of GIST and evaluation of their predictive value. Methods. 54 cases of patients suffering from GIST were enrolled into the study, predominantly in the gastric location. All operated cases had no Imatinib and other chemotherapies up to the day of operation. Expression of targeted proteins was performed by immunohistochemistry and, after that, the results with tabulated clinical data were compared by Kaplan-Meier method and multivariate Cox proportional hazard model of statistical analysis. Results. Our results presented a marked dependence of worsening clinical outcome with high expression CD63 (p = 0.008) as well as with GLUT-1 (p = 0.014). We noted a strict correlation of GLUT-1 expression with CD63 expression (p = 0.03), which could confirm the thesis about the contribution of exosomes in intratumoural hypoxia status. The collected material did not confirm CD9 contribution. Conclusions. As presented here, CD63 and GLUT-1 have a prognostic value in GIST cases. The results confirm the other studies in this scope and can be used in future as an additional prognostic factor.

Gastric gastrointestinal stromal tumor with incomplete duplication cyst - a case with possibility of neoplasia in fetal-period malformed tissues.

The coincidence of GIST and other gastric malignancies are documented well but arising GIST from congenital anomalies is still rarity in literature. To date, only a few papers have been concerned on the possibility of arising neoplasms from duplication cyst of gastrointestinal tract. There, are dominating usual cancers, neuroendocrine cancers or lymphomas but GIST has been noted only once. Here, we report a case of 73 years old female-patient with typical gastric stromal tumor comprised centrally locked an incomplete duplication cyst.

Vulvar angiomyofibroblastoma--a case report of rare entity mimicking Bartholin cyst.

Vulvar angiomyofibroblastoma is rare tumor of obscure histological origin. Here a case of 49-year old woman is described with this intriguing benign vulvar entity. The tumor developed at left vulvar labia and clinically imitated Bartholin cyst with clinical complaints of regional discomfort without pain. A macroscopic evaluation revealed well separated, encapsulated tumor of 3,5 cm in diameter. On cut surface the tumor was whitish, flesh, solid with myxoid appearance without any apparent cysts formation. There were alternating hypo- and hypercellular in the neoplasm. Microscopically the tumor comprised proliferation of small thin walled vessels that were surrounded with cuffs and islands of epithelioid, spindle and plasmacytoid cells with occasional vacuolization. Some aggregations of cells were quite dense and in such fields, vessels were compressed and ecstatic enough to mimic a bit haemangiopericytoma pattern. A production of myxoid intercellular matrix was seen in loose, hypocellular areas and was confirmed by positive pas-alcian blue stain that demonstrated prominent myxoid stroma and intracytoplasmatic globules of acid glicoproteins. The immunoprofile was remarkable enough to show strong expression of vimentin and desmin, while there was a lack of pan-keratin (CKAE1/3) and smooth muscle actin (SMA) immunoreactivities. Such an immunofentype is regarded to share some of myofibrolastic origin despite SMA negativity. Tumor cells seemed to sprout from perivascular regions giving an impression of accumulations strictly associated with neighbouring vascular branches. This configuration of cells is very often viewed as pericyte-like proliferation. Thus, our case of angiomyofibroblastoma is an example of tumor that probably derives from perivascular stem cells that acquire some of myoid features.

Coexistence of renal cell carcinoma of clear cell type with sarcomatoid cell type component and adrenal mature ganglioneuroma with myelolipoma - a case of 69-year-old female patient.

This report presents a case of 69-year-old woman, who was operated due to renal tumor. Apart from renal neoplasm, the adjacent adrenal gland contained another one tumor in medulla of the organ. The renal lesion was diagnosed renal cell carcinoma, clear cell type with undifferentiated cell sarcomatoid component. The adrenal neoplasm was composed of wavy S100-positive, Schwann-like cells and dispersed chromogranin A-reactive ganglion cells to be consistent with mature ganglioneuroma. It was accompanied by coexistent myelolipoma that contained hematopoietic cells including clearly visible megakaryocytes and foci of fat. To our knowledge, our paper is the first to report sporadic clear cell renal cell carcinoma with sarcomatoid cell type component and mature adrenal ganglioneuroma with myelolipoma in the same patient.

Role of immunohistochemical and histochemical profiling in H&E-based diagnosis of scrotal leiomyosarcoma of dartos muscle.

Histochemical and immunohistochemical methods should often but not always complement standardized histopathologic procedures. Here, we illustrate use of these ancillary techniques in a report of scrotal leiomyosarcoma. 62-year-old male patient presented with a palpable, subcutaneous 2,5 cm wide tumor arising from dartos muscle. The tumor was diagnosed leiomyosarcoma G2 pT1b. Interestingly, the sarcomatous mass was focally strictly attached to convoluted, benign bundles of smooth muscles that were intermingled with tumor mass at peripheral, lateral and superior sides of the lesion. We have used immune- and histochemical methods to confirm histopathological findings based on H&E staining. As expected, in tumor cells smooth muscle actin and desmin were strongly immunopositive similarly as Masson trichrome staining, while S100 and CD34 antigens were immunonegative except for sustained positivity for CD34 in vessels. The auxiliary staining methods can provide additional information on the tumorigenesis of leiomyosarcoma. They can also serve to determine additional features of prognostic significance, since e.g. immunoreactivity of CD34 accurately maps vascular density of tumor and enables a careful assessment of vascular invasion in course of leiomyosarcoma as well.