• Publikační typ
• abstrakt z konference MeSH

Primary ovarian mucinous tumors represent a heterogeneous group of neoplasms, and their diagnosis may be challenging. We analyzed 124 primary ovarian mucinous tumors originally diagnosed as mucinous borderline tumors (MBTs) or mucinous carcinomas (MCs), with an emphasis on interobserver diagnostic agreement and the potential for diagnostic support by molecular profiling using a next-generation sequencing targeted panel of 727 DNA and 147 RNA genes. Fourteen experienced pathologists independently assigned a diagnosis from preset options, based on a review of a single digitized slide from each tumor. After excluding 1 outlier participant, there was a moderate agreement in diagnosing the 124 cases when divided into 3 categories (κ = 0.524, for mucinous cystadenoma vs MBT vs MC). A perfect agreement for the distinction between mucinous cystadenoma/MBT as a combined category and MC was found in only 36.3% of the cases. Differentiating between MBTs and MCs with expansile invasion was particularly problematic. After a reclassification of the tumors into near-consensus diagnostic categories on the basis of the initial participant results, a comparison of molecular findings between the MBT and MC groups did not show major and unequivocal differences between MBTs and MCs or between MCs with expansile vs infiltrative pattern of invasion. In contrast, HER2 overexpression or amplification was found only in 5.3% of MBTs and in 35.3% of all MCs and in 45% of MCs with expansile invasion. Overall, HER2 alterations, including mutations, were found in 42.2% of MCs. KRAS mutations were found in 65.5% and PIK3CA mutations in 6% of MCs. In summary, although the diagnostic criteria are well-described, diagnostic agreement among our large group of experienced gynecologic pathologists was only moderate. Diagnostic categories showed a molecular overlap. Nonetheless, molecular profiling may prove to be therapeutically beneficial in advanced-stage, recurrent, or metastatic MCs.

• MeSH
• lidé MeSH
• mucinózní adenokarcinom * diagnóza   genetika   patologie   MeSH
• mucinózní cystadenom * patologie   MeSH
• nádory cystické, mucinózní a serózní * MeSH
• nádory vaječníků * diagnóza   genetika   patologie   MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• Publikační typ
• abstrakt z konference MeSH

Cellular leiomyoma (CL) represents an uncommon variant of uterine leiomyoma with limited data concerning its immunohistochemical and molecular profile. We performed a comprehensive analysis of 52 CL cases all of which were analyzed immunohistochemically. Molecular analysis was possible in 32 cases with sufficient DNA, and 38 cases with sufficient RNA. The immunohistochemical results showed a high expression of smooth muscle markers (calponin (100%), desmin (100%), smooth muscle actin (98.1%), caldesmon (96.1%), transgelin (96.1%), smooth muscle myosin heavy chain (86.5%), and smoothelin (61.5%)). Concerning markers of endometrial stromal differentiation, the expression of CD10 was observed in 65.4% cases (42.2% with H-score > 50), and IFITM1 in 36.5% cases (1.9% with H-score > 50). 36.5% showed HMGA2 overexpression at the IHC level, associated with increased mRNA expression in 14/14 cases. The rearrangement of the HMGA2 gene was detected in 13.2%. Chromosome 1p deletion was found in 19.3%, while 9.4% of tumors showed a pathogenic mutation in the MED12 gene. In conclusion, CL is immunohistochemically characterized by a high expression of "smooth muscle" markers commonly associated with a co-expression of "endometrial stromal" markers, where IFITM1 shows superior performance compared to CD10 regarding its specificity for differentiation from endometrial stromal tumors. The sensitivity of smoothelin in CL seems rather low, but no data is available to assess its specificity. On a molecular level, the most common mutually exclusive aberration in CL affects HMGA2, followed by chromosome 1p deletions and MED12 mutations.

• MeSH
• chromozomy chemie   metabolismus   MeSH
• leiomyom * patologie   MeSH
• lidé MeSH
• mediátorový komplex genetika   metabolismus   MeSH
• mutace MeSH
• nádory dělohy * patologie   MeSH
• nádory endometria * genetika   MeSH
• neprilysin analýza   MeSH
• protein HMGA2 MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

We assessed the value of cytokeratin 17 (CK17) expression for the differential diagnosis between primary ovarian mucinous tumors and metastases from the gastrointestinal tract (GIT) and the significance of CK17 expression in a broad spectrum of primary ovarian tumors with respect to their prognosis. The sample set consisted of 554 primary ovarian tumors and 255 GIT tumors. In the primary ovarian tumors, a higher CK17 expression (in > 10% of tumors cells) was present only in 0-11.4% of all tumors (including mucinous tumors, micropapillary serous borderline tumors, clear cell, endometrioid, and high-grade serous carcinomas). The only exception was low-grade serous carcinoma, where higher CK17 expression was present in 24% of cases. Concerning GIT tumors, the higher levels of CK 17 expression (in > 10% of tumor cells) were observed in the upper GIT tumors (68.5% of pancreatic ductal adenocarcinoma, 61.6% of gallbladder adenocarcinoma, and 46% of gastric adenocarcinoma), which differs substantially not only from most of the primary ovarian tumors, but also from colorectal carcinoma (3.7%; p < 0.001). The results of our study suggest that expression of CK17 can potentially be used as an adjunct marker in differential diagnosis between primary ovarian mucinous tumors and metastases from the upper GIT, but not from colorectal carcinoma. However, in GIT tumors, CK17 can be used in the differential diagnosis between adenocarcinomas of the upper and lower GIT. Statistical analysis did not reveal strong association of CK17 expression with clinicopathological variables or patient outcomes in any primary ovarian tumors.

• MeSH
• adenokarcinom * diagnóza   MeSH
• diferenciální diagnóza MeSH
• gastrointestinální nádory * diagnóza   MeSH
• imunohistochemie MeSH
• keratin-17 MeSH
• kolorektální nádory * diagnóza   MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory slinivky břišní * diagnóza   MeSH
• nádory vaječníků * patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

We report a case of a 49-year-old female with desmoplastic small round cell tumor of the uterus (DSRCT). Histologically, in some areas the tumor showed typical features with ample desmoplastic stroma, while in other areas the tumor cells diffusely infiltrated myometrium with only focal desmoplastic reaction. Immunohistochemically, the tumor cells showed diffuse positivity for desmin, CD56, CD57, EMA and cyclin D1. Focal positivity was present for antibodies against cytokeratin AE1/3, BerEP4, NSE, IFITM1 and CD10. The WT-1 antibody (against the N-terminus) showed cytoplasmic positivity in some tumor cells, while the nuclei were negative. P53 expression was wild-type. The Ki-67 index (MIB1 antibody) was about 55%. Other markers examined including transgelin, myogenin, synaptophysin, chromogranin, h-caldesmon, PAX8, and CD117 were all negative. NGS analysis revealed a fusion transcript of the EWSR1 and WT1 genes. DSRCT of the uterus is a rare neoplasm, as only two cases have been reported so far. However, only one of these cases was examined molecularly with a confirmation of the characteristic EWSR1-WT1 fusion. We report a second case of molecularly confirmed DSRCT of the uterus and discuss its clinical features, differential diagnosis and the significance of molecular testing.

• Publikační typ
• kazuistiky MeSH

Hepatocyte nuclear factor-1-beta (HNF1B) is a transcription factor and putative biomarker of solid tumours. Recently, we have revealed a variety of HNF1B mRNA alternative splicing variants (ASVs) with unknown, but potentially regulatory, functions. The aim of our work was to quantify the most common variants and compare their expression in tumour and non-tumour tissues of the large intestine, prostate, and kidney. The HNF1B mRNA variants 3p, Δ7, Δ7-8, and Δ8 were expressed across all the analysed tissues in 28.2-33.5%, 1.5-2%, 0.8-1.7%, and 2.3-6.9% of overall HNF1B mRNA expression, respectively, and occurred individually or in combination. The quantitative changes of ASVs between tumour and non-tumour tissue were observed for the large intestine (3p, Δ7-8), prostate (3p), and kidney samples (Δ7). Decreased expression of the overall HNF1B mRNA in the large intestine and prostate cancer samples compared with the corresponding non-tumour samples was observed (p = 0.019 and p = 0.047, respectively). The decreased mRNA expression correlated with decreased protein expression in large intestine carcinomas (p < 0.001). The qualitative and quantitative pattern of the ASVs studied by droplet digital PCR was confirmed by next-generation sequencing, which suggests the significance of the NGS approach for further massive evaluation of the splicing patterns in a variety of genes.

• MeSH
• alternativní sestřih * MeSH
• hepatocytární jaderný faktor 1-beta genetika   metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory genetika   metabolismus   MeSH
• polymerázová řetězová reakce MeSH
• protein - isoformy MeSH
• regulace genové exprese u nádorů MeSH
• retrospektivní studie MeSH
• RNA nádorová genetika   metabolismus   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Hodnocení tumor infiltrujících lymfocytů (TIL) nabývá u řady nádorových onemocnění na důležitosti v souvislosti nejen s ohledem na prognózu, ale i na jejich prediktivní význam. Jedním z nádorů, u kterého má hodnocení TIL kromě stanovení prognózy i potenciální dopad na modifikaci léčebných postupů, je karcinom prsu, zejména jeho tzv. triple negativní a HER2 pozitivní varianta. Cílem následujícího sdělení je podat přehled problematiky hodnocení TIL u karcinomu prsu se zaměřením nejen na praktické uplatnění tohoto hodnocení, ale zejména na metodické aspekty hodnocení a reportování výsledků.

Evaluation of tumor infiltrating lymphocytes (TIL) is gaining importance in many cancers not only because of their prognostic, but also predictive significance. One of the tumors in which the evaluation of TIL is of prognostic importance and has potential predictive impact on the modification of treatment procedures is breast cancer, especially its so-called triple negative, and HER2 positive variants.The aim of this review is to provide an overview of the issue of TIL evaluation in breast cancer, focusing not only on the clinical significance of this evaluation, but especially on the methodological aspects of evaluation and standardized reporting of the results.

• MeSH
• lidé MeSH
• nádory prsu * diagnóza   MeSH
• prognóza MeSH
• receptor erbB-2 MeSH
• triple-negativní karcinom prsu * MeSH
• tumor infiltrující lymfocyty MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

Cílem následujícího sdělení je podat přehled problematiky využití imunohistochemických metod u karcinomu endometria. Diskutováno je zejména využití imunohistochemie v diferenciální diagnostice základních histologických typů karcinomu endometria; rozlišení mezi primárním serózním karcinomem endometria a postižením při high grade serózním karcinomu jiného primárního zdroje; v diagnostice nediferencovaného / dediferencovaného karcinomu endometria a v diagnostice nádorů s neuroendokrinní diferenciací. Samostatně je zdůrazněna problematika hodnocení exprese p53 v kontextu diferenciální diagnostiky, ale i prognózy a predikce karcinomu endometria jako pomocného markeru při subtypizaci těchto nádorů.

The goal of this manuscript is to provide an overview of the significance of immunohistochemical methods in diagnosing endometrial carcinoma. The main points discussed include: the use of immunohistochemistry in the differential diagnosis of the main histological types of endometrial carcinoma, the difference between primary serous endometrial carcinoma and the involvement with high grade serous carcinoma of another primary source, the diagnosis of undifferentiated/dedifferentiated endometrial carcinoma, and diagnosing tumours with neuroendocrine differentiation. The role of p53 expression evaluation is also emphasized as a special area of interest, not only in the context of differential diagnosis, but also from the point of view of the prognosis and prediction of endometrial carcinoma as an ancillary marker for subtypization of these tumours.

• MeSH
• diferenciální diagnóza MeSH
• endometroidní karcinom diagnóza   genetika   MeSH
• exprese genu MeSH
• imunohistochemie MeSH
• karcinom * diagnóza   genetika   MeSH
• lidé MeSH
• nádorový supresorový protein p53 MeSH
• nádory endometria * diagnóza   genetika   klasifikace   MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH