Extraskeletal myxoid chondrosarcoma: A study of 17 cases focusing on the diagnostic utility of INSM1 expression and presenting rare morphological variants associated with non-EWSR1::NR4A3 fusions.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain lineage. Insulinoma-associated protein 1 (INSM1) has recently been described as a highly specific and sensitive immunohistochemical marker for EMC. The goal of this study was to evaluate the diagnostic significance of INSM1 immunohistochemistry in EMC. Furthermore, correlations between molecular and morphological findings were performed. Sixteen of 17 EMC cases were stained with the INSM1 antibody. Tumors with at least 5% INSM1-positive cells and any staining intensity were considered positive. Molecular testing was successfully performed in 12/17 cases. The immunohistochemical analysis detected 13 INSM1-positive (81%) and 3 INSM1-negative tumors (19%). The extent of the staining was classified as 1+ in 7 cases (44%), 2+ in 2 cases (13%), 3+ in 2 cases (13%) and 4+ in 2 cases (13%). Intensity of immunostaining was weak in 5 cases (31%), moderate in 2 cases (13%) and strong in 6 cases (38%). Molecular assays revealed 8 EWSR1::NR4A3 positive tumors (67%), 2 TAF15::NR4A3 positive tumors (17%), 1 TCF12::NR4A3 positive tumor (8%) and 1 NR4A3 positive tumor (8%) in which no other gene alteration was identified. Two of them, namely TCF12 positive and one TAF15 positive tumors, were highly cellular and partially associated with pseudopapillary architecture. Our study found that moderate/strong expression of INSM1 in more than 25% of tumor cells was present in only 31% of cases. Thus, the diagnostic utility of INSM1 is rather low. Two morphologically unique cases of non-EWSR1 rearranged EMC with an extremely rare pseudopapillary growth pattern are also reported.

Unique expression patterns of the embryonal stem cell marker SOX2 and hormone receptors suggest the existence of a subpopulation of epithelial stem/progenitor cells in porcine and bovine endometrium.

BACKGROUND: There are currently insufficient data on the population of endometrial epithelial stem/progenitor cells in farm animals. OBJECTIVES: With the aim of identifying a potential population of epithelial stem/progenitor cells in the porcine and bovine endometrium, this study immunohistochemically examined the expression patterns of the oestrogen and progesterone receptors, as well as that of the embryonal stem cell marker SOX2. METHODS: A total of 24 endometrial tissue samples obtained from cycling pigs (n = 12) and cows (n = 12) were included in our study. Each endometrium was divided into basal, middle and luminal portions. The percentage of marker-positive cells and the intensity of the immunoreaction in each portion of the endometrium were determined. RESULTS: Inverse expression patterns of SOX2 and progesterone receptors were found in both animal species throughout the oestrous cycle. Strong diffuse SOX2 expression was detected in the basal portions of the glands, while a significant decrease in positivity and a weak immunoreaction were found in the luminal two thirds of the glandular epithelium. Strong progesterone receptor expression was observed in at least 90% of glandular cells in the middle and luminal portions, whereas weak staining and significant decrease in positivity were detected in the basal portions of the glands. One oestrogen receptor expression pattern resembled that of progesterone receptors. CONCLUSION: The inverse expression patterns of SOX2 and hormone (especially progesterone) receptors suggest that endometrial epithelial stem/progenitor cells represent a subset of cells that reside in the basal portions of the endometrial glands in both the bovine and porcine endometrium.

Effect of psychosocial trauma and stress on sexual dysfunction in women with endometriosis.

BACKGROUND: Endometrial tissue plays an important role in the regulation of female fertility and there is evidence that endometrial pathology (including endometriosis) is closely related to endocrine disorders. On the other hand, various neuroendocrine changes can be significantly affected by psychosocial stress. In connection with these findings, we tested the relationship between neuroendocrine changes, sexual dysfunction, psychosocial/traumatic stress, and dissociative symptoms in women with endometriosis. METHODS: A total of 65 patients with endometriosis were included in the study. Clinical examinations were focused on the biochemical analysis of neuroendocrine markers of endometriosis (cancer antigen 125 [CA 125] and cancer antigen 19-9 [CA 19-9]), estradiol, psychometric evaluation of sexual dysfunction, psychosocial/traumatic stress, and dissociative symptoms. RESULTS: The results showed significant Spearman correlations between the values of the revised range of sexual difficulties for sexual dysfunction (Revised Female Sexual Distress Scale), psychosocial/traumatic stress (Trauma Symptoms Checklist) (R = 0.31), and dissociative symptoms (Somatoform Dissociation Questionnaire) (R = 0.33). Positive correlations were also found between CA 125 and CA 19-9 (R = 0.63), and between CA 125 and the results of the values of the revised scale of sexual difficulties for sexual dysfunction (Revised Female Sexual Distress Scale) (R = 0.29). Also psychosocial/traumatic stress (Trauma Symptoms Checklist) significantly correlated with CA 125 (R = 0.38) and with CA 19-9 (R = 0.33). CONCLUSION: These results represent the first findings regarding the relationship of the neuroendocrine markers CA 125 and CA 19-9 and sexual dysfunction with trauma/stress-related symptoms and dissociative symptoms in women with endometriosis.

Comparative immunohistochemical study of deep infiltrating endometriosis, lymph node endometriosis and atypical ovarian endometriosis including description of a perineural invasion.

AIM: Endometriosis is an inflammatory condition that shares a number of similarities with malignant diseases, such as an abnormal morphology, migration along the nerve bundles and metastatic spread to lymph nodes and distant organs. Endometriotic lesions are associated with oestrogen and progesterone imbalance which seems to play a key role in the pathogenesis of endometriosis. The aim of this study was to compare the status of both oestrogen and progesterone receptors in tissue of deep infiltrating endometriosis, lymph node endometriosis and atypical ovarian endometriosis using immunohistochemical methods, as well as to investigate the relationship between endometriosis and protein p53. METHODS: A total of 40 cases with deep infiltrating endometriosis were included in our study. Based on histopathological analysis of resected specimens, the cases were divided into 2 groups: group 1 - lymph node endometriosis (cases with lymph node involvement; n=12) and group 2 - deep infiltrating endometriosis (cases without lymph node involvement; n=28). As a control group, eutopic endometrium of adenomyosis- and endometriosis-free women were used (n=16). Five cases of atypical ovarian endometriosis as well as descriptions of the nerve involvement in endometriosis were also included. Immunohistochemical staining with a total of 4 markers was performed - oestrogen and progesterone receptors (ER, PR), p53 and Ki-67 (proliferation index). RESULTS: The immunophenotype of the cases in groups 1 and 2 and in the control group was virtually identical in the proliferative phase - strong nuclear ER and PR expression in more than 90% of endometrial glandular and stromal cells. In the early and mid secretory phase, ER expression only slightly decreased (80%) in endometrial glandular cells in group 2 and the control group, whereas in the late secretory phase, significant decrease of ER expression only in the control group was observed (15-50%; P<0.001). In group 2 and the control group, significant decrease of PR expression only in endometrial glandular cells was observed in the mid and late secretory phase (less than 15%; P<0.001). Differences in receptor content were found only in isolated cases in group 2. In group 1, no secretory changes were found. In all three groups, sporadic and weak nuclear p53 expression in less than 3% in both endometrial glandular and stromal cells was detected (regardless of the phase of the menstrual cycle). In atypical ovarian endometriosis, higher and strong p53 expression (on average 26%) and decrease in ER (on average 56%) and PR (less than 1%) expression was observed; compared to the control group and groups 1 and 2, the differences for all 3 markers were highly significant (P<0.001). In all groups, the proliferation index (Ki-67) reached the highest values in the proliferation phase and decreased during the cycle. However, in endometriotic tissue, it was widely variable in the individual phases of the cycle. Perineural spread of endometriosis with significant neural hypertrophy, hyperplasia and involvement of the ganglia of the autonomic nervous system was detected in 5 cases (12.5%). Conlusion. From a histological and immunohistochemical point of view, deep infiltrating endometriosis and lymph node endometriosis appear to represent the same entity. For the first time, a simple immunohistochemical panel with antibodies against ER, PR and p53 useful in diagnosing atypical endometriosis has been described. The marked endometriosis-associated neural changes (endometriotic neuropathy) could be one of the causes of impaired function of the affected organs after debulking surgery with macroscopic negative resection margins as well as pain symptomatology in macroscopic inapparent endometriotic lesions.

Endometriosis and gynaecological cancers: molecular insights behind a complex machinery.

Endometriosis is described as the presence of both endometrial glandular and stromal cells outside the uterine cavity. A major characterization of this disease is ectopic implantation of endometrial cells with increased migration. It is one of the leading causes of morbidity among premenopausal women, with a prevalence of 10-16% of women of reproductive age. Despite over century of intensive research, none of the current treatment options represents a real cure. Based on the current knowledge, endometriosis, particularly its atypical version, is considered to be a transitional form from benign disease to tumour. However, the exact mechanisms of this conversion are still not fully established.

Oncological markers CA-125, CA 19-9 and endometriosis.

The endometrium tissue is functionally androgen related which plays an important role in women's fertility regulation. In addition recent findings show that endometrium related pathology is closely linked to disrupted androgen biosynthesis and associated regulatory functions. These findings also suggest that androgens might play an important role in endometrium related cancer pathology with significant implications for treatment.Based on these findings, we have assessed 50 female outpatients with endometriosis and the clinical investigations were focused on biochemical serum analysis of DHEAS, oncological markers CA-125 and CA 19-9, estradiol, thyreothropic hormone, and prolactin.The results show significant Spearman correlations of CA-125 and CA 19-9 with dehydroepiandrosterone- DHEA-S (R = 0.52 resp. R = 0.49).This result represents 1st reported finding documenting androgen related increase of CA-125 and CA 19-9 levels as significant markers of endometrium pathology and it is possible to assume that these potential biomarkers could have clinical importance with respect to timely diagnosis.

Altered Immunity in Endometriosis: What Came First?

BACKGROUND: This study was conducted to summarize current knowledge of the changes within the immune system, from action of macrophages, lymphocytes and NK cells to biological effects of their products. Endometriosis is a complex gynecological disorder defined as a presence of endometrial tissue outside the uterus affecting over 5 million reproductive-aged women in the U.S. alone. RESULT: In recent years, the potential role of the immune system in the development of endometriosis has increasingly gained attention. Data summarized in our study showed that the most relevant immunocytes are macrophages residing inside the peritoneal cavity and the ratios of Th1 to Th2 cells. Another crucial immunological parameter is the balance in production of cytokines and chemoatractants. CONCLUSIONS: This review confirms that despite decades of intensive research, the involvement of the immune system remains elusive, as we can recognize the changes, but still do not understand if these changes represent the results of endometriosis or if they are contributing factors. Based on these findings, we also discuss new treatment possibilities.