Loss of oestrogen receptor (ER) and progesterone receptor (PR) expression in endometrial cancer cells indicates poor prognosis. The aim of this study was to determine the correlation of ER and PR expression in cancer cells and the surrounding myometrium with the disease progression. Immunohistochemical expression of ER and PR was detected in cancer and myometrial cells of patients with EC. ER was detected in 65.2% of cancer cells and in 88.4% of myometrial cells. PR was detected in 59.4% of cancer cells and in 84.1% of myometrial cells. The 5-year overall survival (OS) was 76.8%. Patients with ER and PR negative EC had a shorter period until recurrence (p = .013 and .043) and shorter OS (p = .011 and .066) than those with ER and PR positive cancer. Negative ER and PR status in EC has an impact on recurrence and poor OS. The status of hormone receptors in myometrium may be useful in disease prognosis. Impact Statement The status of hormone receptors in endometrial cancer has been the subject of numerous studies and loss of hormone receptors indicates higher tumor grade and higher clinical stage, lympho-vascular space invasion and deeper myometrial invasion. Although, the communication between the endometrium and myometrium is crucial under physiological conditions, the status of hormone receptors in the myometrium and its significance in cancer progression is poorly studied. Our results showed that loss of ER in the myometrium indicate poor prognosis. The assessment of hormone receptor status in myometrium might be useful in predicting the course of the disease. Results of our research support the theory that stromal and myometrial cells may contribute to tumorigenesis in endometrial cancer. Better understanding of ER/PR expression in myometrial cells is needed, and our research opens new possibilities for identification of key pathways and new potential target molecules in EC prognosis and treatment. It is probable that future classification of endometrial cancer will rely on molecular sub-typing, where the status of hormone receptors in the myometrium might play an important role.

Breast cancer, the most frequent disease amongst women worldwide, accounts for the highest cancerrelated mortality rate. Triple-negative breast cancer (TNBC) subtype encompasses ~15% of all breast cancers and lack estrogen, progesterone, and HER2 receptors. Although risk factors for breast cancer are well-known, factors underpinning breast cancer onset and progression remain unknown. Recent studies suggest the plausible role of oncoviruses including human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and mouse mammary tumor virus (MMTV) in breast cancer pathogenesis. However, the role of these oncoviruses in TNBC is still unclear. In the current study, we explored the status of high-risk HPVs, EBV, and MMTV in a well-defined TNBC cohort from Croatia in comparison to 16 normal/non TNBC samples (controls) using polymerase chain reaction assay. We found high-risk HPVs and EBV present in 37/70 (53%) and 25/70 (36%) of the cases, respectively. The most common HPV types are 52, 45, 31, 58 and 68. We found 16% of the samples positive for co-presence of high-risk HPVs and EBV. Moreover, our data revealed that 5/70 (7%) samples are positive for MMTV. In addition, only 2/70 (3%) samples had copresence of HPVs, EBV, and MMTV without any significant association with the clinicopathological variables. While, 6/16 (37.5%) controls were positive for HPV (p = .4), EBV was absent in all controls (0/ 16, 0%) (p = .01). In addition, we did not find the co-presence of the oncoviruses in the controls (p > .05). Nevertheless, further investigations are essential to understand the underlying mechanisms of multipleoncogenic viruses' interaction in breast carcinogenesis, especially TNBC.

INTRODUCTION: Croatia launched the National program for the early detection of breast cancer (BC) in 2006. The program targets women between the age of 50 and 69 to take a mammogram every two years. About 60% of women performed mammography through the program. The study aimed to determine the difference in breast cancer's pathohistologic features before and after the introduction of screening. MATERIALS AND METHODS: Data was collected retrospectively in a single high volume center for women diagnosed with invasive BC in the period before the introduction of mammography screening (2005-2007; N=1833), and from newly diagnosed (2017-2019; N=2676). Statistical significance of the findings was evaluated using Chi square test. RESULTS: We recorded a 31.5% increase in the number of patients referred to our hospital in the post-screening period. However, no statistically significant reduction in tumor size, histological grade or the number of positive axillary lymph nodes was detected in newly diagnosed BC compared to those diagnosed over ten years ago. The mean age of BC incidence was 61 years, with the mean tumor size of 22 mm (median 18 mm), in both periods. The significant difference occurred in the distribution of the intrinsic subtypes of BC (P<.001). About 45% of patients were diagnosed with pT1N0 stage, in both periods. CONCLUSION: In the post-screening period, we treated 32% more newly diagnosed breast cancers. However, pathohistological features of BC, along with the average tumor size, did not change.

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