Complex immunohistochemical and molecular study on 5 cases of ovarian juvenile granulosa cell tumors reveals a consistent alteration in the PI3K/AKT/mTOR signaling pathway.

Background: Juvenile granulosa cell tumor (JGCT) of the ovary is a rare tumor with distinct clinicopathological and hormonal features primarily affecting young women and children. We conducted a complex clinicopathological, immunohistochemical, and molecular analysis of five cases of JGCT.

Methods: The immunohistochemical examination was performed with 32 markers, including markers that have not been previously investigated.

An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers.

The current knowledge about the immunohistochemical features of adult granulosa cell tumor (AGCT) is mostly limited to the "traditional" immunohistochemical markers of sex cord differentiation, such as inhibin, calretinin, FOXL2, SF1, and CD99. Knowledge about the immunohistochemical markers possibly used for predictive purpose is limited. In our study, we focused on the immunohistochemical examination of 290 cases of AGCT classified based on strict diagnostic criteria, including molecular testing.

HER2 status as a potential predictive biomarker for ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian carcinoma characterized by unique biological features and highly malignant characteristics including low chemosensitivity. Therefore, new therapeutic targets are needed. These could include the downstream pathways of receptor tyrosine kinases, especially the human epidermal growth factor receptor 2 (HER2).

Lynch syndrome-associated upper tract urothelial carcinoma frequently occurs in patients older than 60 years: an opportunity to revisit urology clinical guidelines.

Upper tract urothelial carcinoma (UTUC) is the third most common malignancy associated with Lynch syndrome (LS). The current European urology guidelines recommend screening for LS in patients with UTUC up to the age of 60 years. In this study, we examined a cohort of patients with UTUC for potential association with LS in order to establish the sensitivity of current guidelines in detecting LS.

Immunohistochemical expression of PRAME in 485 cases of epithelial tubo-ovarian tumors.

Preferentially expressed antigen of melanoma (PRAME) is a cancer/testis antigen selectively expressed in somatic tissues and various solid malignant tumors and is associated with poor prognostic outcome. Our research aimed to comprehensively compare its expression in a large cohort of tubo-ovarian epithelial tumors and examine its correlation with our clinico-pathologic data, as well as to assess its potential use in diagnostics and therapy.We examined 485 cases of epithelial tubo-ovarian tumors including 107 clear cell carcinomas (CCC), 52 endometroid carcinomas (EC), 103 high grade serous carcinomas (HGSC), 119 low grade serous carcinomas (LGSC)/micropapillary variant of serous borderline tumors (mSBT), and 104 cases of mucinous carcinomas (MC)/mucinous borderline tumors (MBT).

Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance.

In gynecological neoplasms, immunohistochemical (IHC) expression of p53 is generally an accurate predictor of TP53 mutation status if correctly interpreted by the pathologist. However, the literature concerning cut-offs, frequency and prognostic significance of p53 staining in ovarian mucinous tumours is limited and heterogeneous. We performed an analysis of 123 primary ovarian mucinous tumours including mucinous borderline tumours (MBT), mucinous carcinomas (MC), and tumours with equivocal features between MBT and MC.

Microsatellite instability in non-endometrioid ovarian epithelial tumors: a study of 400 cases comparing immunohistochemistry, PCR, and NGS based testing with mutation status of MMR genes.

Testing of microsatellite instability is not only used as a triage for possible Lynch syndrome, but also to predict immunotherapy treatment response. The aim of this study was to assess the frequency of mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) in 400 cases of non-endometrioid ovarian tumors (high-grade serous, low-grade serous, mucinous and clear cell), to compare different methodological approaches of testing, and to assess the optimal approach for next generation sequencing (NGS) MSI testing. For all tumors, we evaluated immunohistochemical (IHC) expression of MMR proteins and assessed microsatellite markers by PCR-based method.

Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories.

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.

A comprehensive immunohistochemical analysis of IMP2 and IMP3 in 542 cases of ovarian tumors.

Background: IMP2 and IMP3 are mRNA binding proteins involved in carcinogenesis. We examined a large cohort of ovarian tumors with the aim to assess the value of IMP2 and IMP3 for differential diagnosis, and to assess their prognostic significance.

Methods: Immunohistochemical analyses with antibodies against IMP2 and IMP3 were performed on 554 primary ovarian tumors including 114 high grade serous carcinomas, 100 low grade serous carcinomas, 124 clear cell carcinomas, 54 endometrioid carcinomas, 34 mucinous carcinomas, 75 mucinous borderline tumors, and 41 serous borderline tumors (micropapillary variant).

BDNF, sHLA-G, and sTREM-1 are useful blood biomarkers for identifying grade IV glioma patients.

Inflammation and immunity belong to the main factors influencing tumor growth. In this study, we attempted to identify a profile of biomarkers associated with gliomas. We found decreased serum levels of sTREM-1 (soluble triggering receptor expressed on myelocytes) and increased levels of IL-10 in all grades of glioma patients in comparison with healthy controls (sTREM-1: grade II: p=0.

HLA-G 14bp Ins/Del Polymorphism, Plasma Level of Soluble HLA-G, and Association with IL-6/IL-10 Ratio and Survival of Glioma Patients.

HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group.

The cytokeratin 17 expression in primary ovarian tumors has diagnostic but not prognostic significance.

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.

5'URR regulatory polymorphisms are associated with the risk of developing gliomas.

Background: Human leukocyte antigen G (HLA-G) belongs to non-classical MHC class I molecules that is involved in the suppression of immune response. As HLA-G plays important role in the maintenance of fetal tolerance, its overexpression has been associated with tumor progression. For the regulation of HLA-G levels, genetic variants within the 5' upstream regulatory region (5'URR) are of crucial importance.

Significance of transcriptionally-active high-risk human papillomavirus in sinonasal squamous cell carcinoma: Case series and a meta-analysis.

Sinonasal cancers represent a highly heterogeneous group of head and neck cancers, for which etiological and prognostic significance of high-risk human papillomavirus (HPV) infections has not yet been conclusively established. We investigated the presence of transcriptionally-active high-risk HPV in a series of 34 sinonasal squamous cell cancer (SNSCC) cases and evaluated the effect of transcriptionally-active HPV on the overall survival. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the prevalence of HPV positivity across histological subtypes of SNSCC.

TREM-1 and TREM-2 Expression on Blood Monocytes Could Help Predict Survival in High-Grade Glioma Patients.

Objective: In recent years, the role of the modern inflammatory markers TREM-1 (triggering receptors expressed on myeloid cells) and HMGB1 (high mobility group box 1 protein) in tumorigenesis has begun to be studied. Their role in gliomas is not clear. The aim of our study was to find the role of inflammation in gliomas.

Targeted next generation sequencing of MLH1-deficient, MLH1 promoter hypermethylated, and BRAF/RAS-wild-type colorectal adenocarcinomas is effective in detecting tumors with actionable oncogenic gene fusions.

Oncogenic gene fusions represent attractive targets for therapy of cancer. However, the frequency of actionable genomic rearrangements in colorectal cancer (CRC) is very low, and universal screening for these alterations seems to be impractical and costly. To address this problem, several large scale studies retrospectivelly showed that CRC with gene fusions are highly enriched in groups of tumors defined by MLH1 DNA mismatch repair protein deficiency (MLH1d), and hypermethylation of MLH1 promoter (MLH1ph), and/or the presence of microsatellite instability, and BRAF/KRAS wild-type status (BRAFwt/KRASwt).

Solitary fibrous tumors of the head and neck region revisited: a single-institution study of 20 cases and review of the literature.

A solitary fibrous tumor (SFT) is a rare, NAB2-STAT6 fusion gene-associated mesenchymal neoplasm. It most commonly arises in the pleural site, but it can occur at many other sites, and rarely also in the head and neck (H&N) region. STFs may show many growth patterns and therefore can be easily mistaken for other more common H&N spindle cell or epithelial lesions.

Fibro-osseous pseudotumor of digits and myositis ossificans show consistent COL1A1-USP6 rearrangement: a clinicopathological and genetic study of 27 cases.

Myositis ossificans (MO) and fibro-osseous pseudotumor of digits (FOPD) are localized, self-limiting bone-producing pseudosarcomatous lesions characterized by nodular fasciitis-like proliferation and osteoid and immature woven bone production, which may eventually develop into more mature lamellar bone. Traditionally, MO and FOPD were thought to be of reactive, non-neoplastic nature. USP6 gene rearrangement was recently reported as a consistent finding in MO and FOPD, thus expanding the spectrum of transient, USP6-rearranged neoplasms.

Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens.

Pulmonary small cell carcinoma (SCLC) can be usually diagnosed based on the morphological evaluation of routine histological or cytological preparations. However, immunohistochemistry may be also necessary in problematic cases. Insulinoma-associated 1 (INSM1) has recently been reported as a highly sensitive and specific marker that displays positivity in ~90%-100% of poorly differentiated pulmonary neuroendocrine tumors.

P16 is a useful supplemental diagnostic marker of pulmonary small cell carcinoma in small biopsies and cytology specimens.

Pulmonary small cell carcinoma (SCLC) is usually diagnosed in small biopsy or cytological specimens based on cytomorphology; however in ambiguous cases diagnosis requires additional support by immunohistochemistry. While TP53 and RB1 alterations with secondary overexpression of p16 are mainstay events in SCLC pathogenesis, diagnostic value of p16-positivity in the diagnosis of SCLC has not yet been fully investigated. We examined the expression of p16, CD56, synaptophysin (SYP), chromogranin A and thyroid transcription factor-1 (TTF1) in a series of pulmonary and extrapulmonary small cell carcinomas, pulmonary carcinoids and non-small cell lung carcinomas, and compared diagnostic performance of these markers in the diagnosis of SCLC.

Endometrial Endometrioid Carcinoma With Large Cystic Growth Configuration and Deceptive Pattern of Invasion Associated With Abundant Nodular Fasciitis-like Stroma: A Unique Hitherto Unreported Histology in Endometrioid Carcinoma.

We describe a case of an unusual endometrial endometrioid carcinoma occurring in a 67-year-old woman. The tumor involved uterine corpus as well as lower uterine segment and presented as polypoid tumor protruding through the cervical orifice. Microscopically, the tumor was characterized by broad zones of cytologically bland fibromyxoid stroma resembling nodular fasciitis, showing vaguely nodular architecture.

Hormone receptor status of contralateral breast cancers: analysis of data from the US SEER population-based registries.

Background: Women diagnosed with breast cancer display higher propensity to develop second primary cancer in the contralateral breast (CBC). Identification of patients with increased risk of CBC and understanding relationships between hormone receptor (HR) statuses of the first and second breast cancers is desirable for endocrine-based prevention strategies.

Methods: Using 1992-2012 data from 13 SEER registries, the risk of developing CBC was determined as ratio of observed and expected second breast cancers (SIR).

Human papillomavirus infection and p16 expression in the immunocompetent patients with extragenital/extraungual Bowen's disease.

Background: The role of human papillomaviruses (HPV) in the development of squamous cell carcinoma (SCC) has been established for anogenital lesions but still remains controversial for carcinomas in other sites. The aim of this study was to determine the α-HPV and β-HPV prevalence and their association with p16 expression, sun exposure, and clinicopathological findings in patients with Bowen's disease (BD).

Methods: One hundred sixty nine skin biopsy specimens from 157 immunocompetent patients with extragenital/extraungual BD were examined for HPV status and p16 expression.