Marcin Bobiński

Genetic analysis of uterine aspirates improves the diagnostic value and captures the intra-tumor heterogeneity of endometrial cancers

Endometrial cancer is the most common cancer of the female genital tract in developed countries. Although the majority of endometrial cancers are diagnosed at early stages and the 5-year overall survival is around 80%, early detection of these tumors is crucial to improve the survival of patients given that the advanced tumors are associated with a poor outcome. Furthermore, correct assessment of the pre-clinical diagnosis is decisive to guide the surgical treatment and management of the patient. In this sense, the potential of targeted genetic sequencing of uterine aspirates has been assessed as a pre-operative tool to obtain reliable information regarding the mutational profile of a given tumor, even in samples that are not histologically classifiable. A total of 83 paired samples were sequenced (uterine aspirates and hysterectomy specimens), including 62 endometrioid and non-endometrioid tumors, 10 cases of atypical hyperplasia and 11 non-cancerous endometrial disorders. Even though diagnosing endometrial cancer based exclusively on genetic alterations is currently unfeasible, mutations were mainly found in uterine aspirates from malignant disorders, suggesting its potential in the near future for supporting the standard histologic diagnosis. Moreover, this approach provides the first evidence of the high intra-tumor genetic heterogeneity associated with endometrial cancer, evident when multiple regions of tumors are analyzed from an individual hysterectomy. Notably, the genetic analysis of uterine aspirates captures this heterogeneity, solving the potential problem of incomplete genetic characterization when a single tumor biopsy is analyzed.

Neuropilin 1 in uterine leiomyosarcoma. Clinical and pathological analysis

OBJECTIVES The role of angiogenesis in leiomyosarcomas still remains unclear. The aim of this study was to evaluate the NRP1 expression in the leiomyosarcoma tissues and to find the relations between its expression and the clinical features. MATERIAL AND METHODS The study group consisted of 50 patients with diagnosis of the uterine leiomyosarcoma. Clinical and follow up data were collected. Using immunohistochemical methods the expression of NRP1 was detected. RESULTS The lack of NRP1 expression was found in 14 cases, positive (weak or moderate) expression was noted in 36 cases. The significantly higher expression of NRP1 was observed in more severe clinical stages in comparison to lower stages of the disease. The significantly shorter survival of patients with the positive expression of NRP1 in leiomyosarcoma was observed. CONCLUSIONS The expression of NRP1 is associated with clinical advancement and worse prognosis in uterine LMS. Neuropilin 1 can be widely used as a postoperative survival predictor for the patients suffering from uterine LMS.

Blood-based analyses of cancer: Circulating myeloid-derived suppressor cells – is a new era coming?

Abstract Progress in cancer treatment made by the beginning of the 21st century has shifted the paradigm from one-size-fits-all to tailor-made treatment. The popular vision, to study solid tumors through the relatively noninvasive sampling of blood, is one of the most thrilling and rapidly advancing fields in global cancer diagnostics. From this perspective, immune-cell analysis in cancer could play a pivotal role in oncology practice. This approach is driven both by rapid technological developments, including the analysis of circulating myeloid-derived suppressor cells (cMDSCs), and by the increasing application of (immune) therapies, the success or failure of which may depend on effective and timely measurements of relevant biomarkers. Although the implementation of these powerful noninvasive diagnostic capabilities in guiding precision cancer treatment is poised to change the ways in which we select and monitor cancer therapy, challenges remain. Here, we discuss the challenges associated with the analysis and clinical aspects of cMDSCs and assess whether the problems in implementing tumor-evolution monitoring as a global tool in personalized oncology can be overcome.

Does the patients age at cancer diagnosis affect microvessels density in uterine sarcoma tissues

OBJECTIVES The objective of the study was to retrospectively evaluate the density of vessels exhibiting positive glycoprotein CD34 expression in the uterine leiomyosarcoma tissues and their correlation with the age of patients at the time of tumor diagnosis. MATERIAL AND METHODS The archival paraffin blocks with the cancer tissues collected from 50 patients suffering from uterine leiomyosarcoma were used together with their clinical and demographic data. The immunohistochemical peroxidase-de-pendent methods were used to detect microvessels with positive CD34 expression. The glycoprotein CD34 expression was evaluated as a density of microvessel showing the positive immunohistochemical reaction (MVDCD34). RESULTS The negative, statistically significant correlation between the age of patients (at the moment diagnosis) and the MVDCD34+ (R = -0.289, p = 0.042) was found. CONCLUSIONS The studys findings may suggest that the tissues of younger people constitute a permissive environment for pro-angiogenic factors.

Abstract 162: Genomic analysis of uterine aspirates improves diagnosis and captures the intratumor heterogeneity in endometrial cancer

Background: Endometrial cancer (EC) is the most common cancer in female genital tract in developed countries. Although the majority of ECs are diagnosed in early stages, with a 5-year overall survival of around 80%, an early detection of these tumors is crucial to increase survival of patients given that advanced tumors are associated with poorer outcome. Furthermore, the correct assessment of pre-clinical diagnosis is also decisive to guide the surgical management and treatment of the patient. Results: Genetic analysis of uterine aspirates identifies the mutational profile of endometrial cancers and represents the intra-tumor heterogeneity found in the analysis of multiple tumor regions from hysterectomy. Conclusions: The current study reveals the potential of the genetic analysis of uterine aspirates as a pre-operative tool to diagnosis, even in biopsies with insufficient material, with a sensitivity of 93.7% and a specificity of 91.7%. Additionally, genetic analysis of uterine aspirates allows to capture the intra-tumor heterogeneity identified in ECs. Citation Format: Alba Mota, Eva Colas, Pablo Garcia-Sanz, Irene Campoy, Alejandro Rojo-Sebastian, Luis Chiva, Sonsoles Alonso, Sonia Gatius, Antonio Gil-Moreno, Xavier Gonzalez-Tallada, Berta Diaz-Feijoo, Patrycja Ziober Malinwska, Marcin Bobinski, Jaume Reventos, Xavier Matias-Guiu, Gema Moreno-Bueno. Genomic analysis of uterine aspirates improves diagnosis and captures the intratumor heterogeneity in endometrial cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 162.

Microvessels Density in Uterine Leiomyosarcoma

Uterine leiomyosarcomas (LMS) are rare tumors typically presenting rapid growth and unfavorable outcome. Nowadays the results of uterine LMS treatment do not meet expectations. Angiogenesis is one of processes investigated to be target for future treatment. The aim of the research was to assess microvessels density (MVD) in tumor samples collected from 50 patients with histological confirmed uterine leiomyosarcoma and to investigate statistical relations between MVD, patients survival, and FIGO stage of tumor. The assessment was carried out using immunohistochemistry methods with anti-CD34 antibody. No significant difference in MVD between FIGO stages was observed. Furthermore, contrary to many other malignancies, we found no significant relation between MVD and patients overall and 2-year survival. Results obtained in the study suggest that processes on vascular mimicry and mesenchymal to epithelial transition (MET) may play important role in development of LMS. No statistical relation between MVD and survival leads to conclusion that not only angiogenesis but other mechanisms as well should be taken into consideration in planning future research.

Nierówności w zdrowiu w świetle wyników projektu „problem zgłaszalności kobiet na badania cytologiczne w Polsce. Próba analizy socjomedycznej”

Projekt zostal sfinansowany ze środkow Narodowego Centrum Nauki przyznanych na pod- stawie decyzji numer DEC-2011/03/B/HS6/04503.