Developmental Cues and Molecular Drivers in Myelinogenesis: Revisiting Early Life to Re-Evaluate the Integrity of CNS Myelin.

The mammalian central nervous system (CNS) coordinates its communication through saltatory conduction, facilitated by myelin-forming oligodendrocytes (OLs). Despite the fact that neurogenesis from stem cell niches has caught the majority of attention in recent years, oligodendrogenesis and, more specifically, the molecular underpinnings behind OL-dependent myelinogenesis, remain largely unknown. In this comprehensive review, we determine the developmental cues and molecular drivers which regulate normal myelination both at the prenatal and postnatal periods. We have indexed the individual stages of myelinogenesis sequentially; from the initiation of oligodendrocyte precursor cells, including migration and proliferation, to first contact with the axon that enlists positive and negative regulators for myelination, until the ultimate maintenance of the axon ensheathment and myelin growth. Here, we highlight multiple developmental pathways that are key to successful myelin formation and define the molecular pathways that can potentially be targets for pharmacological interventions in a variety of neurological disorders that exhibit demyelination.

Altered Distribution and Expression of Syndecan-1 and -4 as an Additional Hallmark in Psoriasis.

Syndecans act as independent co-receptors to exert biological activities and their altered function is associated with many pathophysiological conditions. Here, syndecan-1 and -4 were examined in lesional skin of patients with psoriasis. Immunohistochemical staining confirmed altered syndecan-1 distribution and revealed absence of syndecan-4 expression in the epidermis. Fibronectin (FN)-known to influence inflammation and keratinocyte hyperproliferation via α5ß1 integrin in psoriasis-was also decreased. Syndecan-1 and -4 expression was analyzed in freshly isolated lesional psoriatic human keratinocytes (PHK) characterized based on their proliferation and differentiation properties. mRNA levels of syndecan-1 were similar between healthy and PHK, while syndecan-4 was significantly decreased. Cell growth and release of the pro-inflammatory Tumor Necrosis Factor-alpha (TNFα) were selectively and significantly induced in PHKs plated on FN. Results from co-culture of healthy keratinocytes and psoriatic fibroblasts led to the speculation that at least one factor released by fibroblasts down-regulate syndecan-1 expression in PHK plated on FN. To assay if biological treatments for psoriasis target keratinocyte proliferation, gelatin-based patches enriched with inteleukin (IL)-17α or TNFα blockers were prepared and tested using a full-thickness healthy epidermal model (Phenion®). Immunohistochemistry analysis showed that both blockers impacted the localisation of syndecan-1 within the refined epidermis. These results provide evidence that syndecans expression are modified in psoriasis, suggesting that they may represent markers of interest in this pathology.

Protein expression pattern of tissue inhibitor of metalloproteinase-3 (TIMP3) in endometriosis and normal endometrium.

Given the involvement of different extracellular matrix (ECM) metalloproteinases (MMPs) in endometriosis, the protein expression pattern of tissue inhibitor of metalloproteinase-3 (TIMP3) was analyzed in this study in endometriosis and normal endometrium. Tissue samples were collected prospectively from 64 premenopausal patients undergoing operative laparoscopy. Protein expression of TIMP3 was analyzed immunohistochemically in endometriotic lesions (n = 30) and normal eutopic endometrium from patients with (n = 35) and without (n = 29) endometriosis. Comparison between the three different groups of tissue samples showed that TIMP3 was differentially expressed between the three groups (p = .04). Pair-wise comparisons showed that TIMP3 expression was lower in endometriotic lesions as compared with normal eutopic endometrium from controls (p = .006); the same non-significant trend was found, in the comparison between endometriosis lesions and matched eutopic endometrium. There were no differences in TIMP3 expression in the normal eutopic endometrium between patients with and without endometriosis. In conclusion, TIMP3 seems to be involved in the pathogenesis, pathophysiology, and maintenance of endometriosis and it might be useful as a diagnostic and prognostic marker of endometriosis. Future studies should further investigate this issue, as well as the interplay between TIMPs and different extracellular MMPs in endometriosis.

Recurrent complete hydatidiform mole: where we are, is there a safe gestational horizon? Opinion and mini-review.

Benign hydatidiform mole, complete or partial, is the most common type of gestational trophoblastic disease (GTD) characterised by excessive trophoblastic proliferation and abnormal embryonic development. Although most complete hydatidiform moles (CHMs) are diploid androgenetic, a few cases of CHMs are biparental, characterised by recurrence and familial clustering. In these rare cases, mutations in NLRP7 or KHDC3L genes, associated with maternal imprinting defects, have been implicated. Current data regarding future pregnancy options in hydatidiform moles are discussed and our opinion is presented based on an incidence that took place in our hospital with a woman with consecutive molar pregnancies. In recurrent hydatidiform moles, DNA testing should be performed and when NLRP7 or KHDC3L mutation are detected, oocyte donation should be proposed as an option to maximise woman's chances of having a normal pregnancy.

The Impact of Lifestyle on the Secondary Sex Ratio: A Review.

The secondary sex ratio (SSR), indicating the ratio of male to female live births, has garnered considerable attention within the realms of reproductive biology and public health. Numerous factors have been posited as potential trendsetters of the SSR. Given the extensive research on the impact of daily behaviors and habits on individuals' reproductive health, there is a plausible suggestion that lifestyle choices may also influence the SSR. By synthesizing the existing literature on the current research field, this comprehensive review indicates that an elevated SSR has been associated with an increased intake of fatty acids and monosaccharides, proper nutrition, higher educational levels, financial prosperity, and favorable housing conditions. On the other hand, a decreased SSR may be linked to undernutrition, socioeconomic disparities, and psychological distress, aligning with the Trivers-Willard hypothesis. Occupational factors, smoking habits, and cultural beliefs could also contribute to trends in the SSR. Our review underscores the significance of considering the aforementioned factors in studies examining the SSR and emphasizes the necessity for further research to unravel the mechanisms underpinning these connections. A more profound comprehension of SSR alterations due to lifestyle holds the potential to adequately develop public health interventions and healthcare strategies to enhance reproductive health and overall well-being.

The immunohistochemical expression of CD24 and CD171 adhesion molecules in borderline ovarian tumors.

CD24 and CD171 are cell adhesion proteins, which have been shown to be overexpressed in several carcinomas and to be associated with a poor clinical outcome. Our aim was to determine the expression of these two adhesion molecules in ovarian borderline neoplasms. We investigated 50 ovarian borderline tumors (serous, mucinous and endometrioid) as well as 29 benign cystadenomas and 25 carcinomas, which were used as controls. Paraffin sections were stained immunohistochemically for CD24 and CD171, and their expression was recorded in a semi-quantitative manner. In normal epithelium and benign ovarian cystadenomas both the CD24 and CD171 expression was negative to low, while their expression was significantly increased in borderline and malignant ovarian tumors. High-grade carcinomas, and carcinomas with metastases to the omentum presented considerably higher CD24 expression than low-grade carcinomas, and carcinomas without metastases. In addition, a few borderline and many malignant tumors presented cytoplasmic CD24 immunoreactivity, whereas all benign and most borderline tumors showed apical localization of this molecule. In conclusion, borderline tumors and carcinomas of the ovary present increased expression of CD24 and CD171 in relation to their benign counterparts, as is the case in malignant tumors of other organs. Change of staining pattern of CD24 (apical to cytoplasmic) apparently relates to a more aggressive phenotype.

Addressing Spaceflight Biology through the Lens of a Histologist-Embryologist.

Embryogenesis and fetal development are highly delicate and error-prone processes in their core physiology, let alone if stress-associated factors and conditions are involved. Space radiation and altered gravity are factors that could radically affect fertility and pregnancy and compromise a physiological organogenesis. Unfortunately, there is a dearth of information examining the effects of cosmic exposures on reproductive and proliferating outcomes with regard to mammalian embryonic development. However, explicit attention has been given to investigations exploring discrete structures and neural networks such as the vestibular system, an entity that is viewed as the sixth sense and organically controls gravity beginning with the prenatal period. The role of the gut microbiome, a newly acknowledged field of research in the space community, is also being challenged to be added in forthcoming experimental protocols. This review discusses the data that have surfaced from simulations or actual space expeditions and addresses developmental adaptations at the histological level induced by an extraterrestrial milieu.

Leydig cell hyperplasia as a cause of virilization in a postmenopausal woman: A case report.

Virilization is a rare condition in postmenopausal women, usually attributed to androgen excess of ovarian or adrenal origin. A 62-year-old woman presented with excessive hair loss of 3 months' duration and was investigated for an endocrine cause of alopecia. The hormonal evaluation revealed increased testosterone but normal levels of androstenedione and dehydroepiandrosterone sulfate, while the results of transvaginal ultrasonography and abdominal computed tomography were unremarkable. Based on these findings, the possibility of an adrenal androgen-secreting tumor was ruled out and suspicion of Leydig cell hyperplasia was raised. A bilateral laparoscopic salpingo-oophorectomy was performed due to the age of the patient and the diagnosis of Leydig cell hyperplasia was confirmed by histopathological examination. The postoperative course of the patient was uneventful and a repeat hormonal evaluation after the operation showed a normalization of androgen levels. In conclusion, Leydig cell hyperplasia should be considered as a likely cause of hyperandrogenism of ovarian origin in women who develop virilization. In postmenopausal women, bilateral oophorectomy will treat the disorder and provide a conclusive diagnosis via histopathological examination.

Co-Existence of Endometriosis with Ovarian Dermoid Cysts: A Retrospective Cohort Study.

Both endometriosis and ovarian dermoid cysts are benign conditions characterized by the presence of well-differentiated tissues in ectopic locations. The presence and surgical excision of these entities can potentially impact ovarian reserves, contributing to reduced chances of future pregnancy. The objective of our study is to investigate the bidirectional association between endometriosis and ovarian dermoid cysts, as well as to analyze the clinical characteristics of patients diagnosed with both conditions. A retrospective cohort study was conducted, including women who underwent laparoscopy and received histological diagnoses of endometriosis and/or dermoid cysts between 2011 and 2019 at the Cantonal Hospital of Schaffhausen. We identified 985 women with endometriosis and 83 women with ovarian dermoid cysts. Among these groups, 22 women presented with both endometriosis and ovarian dermoid cysts. The majority of the above patients had endometriosis stage rASRM I-II (72.7%), with peritoneal endometriosis being the most common phenotype of endometriosis (77.2%). Out of the 14 patients with a desire for future pregnancy, the majority (11/14, 78.5%) had an EFI score of 7-8. The prevalence of bilateral ovarian dermoid cysts was higher in women with both ovarian dermoid cysts and endometriosis in comparison to women with ovarian dermoid cysts without endometriosis (18% vs. 6.5%). Our study revealed that 26.5% of women with ovarian dermoid cysts also had endometriosis, a notably higher prevalence than observed in the general population. Clinicians should be aware of this co-existence, and preoperative counseling should be an integral part of the care plan for affected individuals, where the potential risks and the available options for fertility preservation should be discussed in detail.

Effect of N-acetyl-L-cysteine on inflammation after intraperitoneal mesh placement in a potentially contaminated environment: An experimental study in the rat.

BACKGROUND: The use of prosthetic meshes in abdominal wall reconstruction is a well-established approach; however, in certain cases where a bowel resection coexists its application is disputed. Any underlying inflammatory process may augment adhesion formation which is a major postoperative complication. In this animal study, our aim was to investigate the effect of N-acetyl-l-cysteine (NAC) on adhesion formation and the expression of inflammatory markers when a mesh was used in a clean or a potentially contaminated environment. METHODS: Sixty male Wistar rats were randomly and equally allocated in 3 groups: A, B and C. Animals in all groups underwent laparotomy, a prosthetic mesh was placed and chemoprophylaxis with ciprofloxacin was administered. In groups B and C an enterectomy was also performed. NAC was injected intraperitoneally in group C. Adhesion formation, IL-1a, IL-6, TNF-a and histological data including fibrosis, neutrophils' infiltration and neovascularization were assessed. Mesh samples were sent for cultivation. RESULTS: Adhesion formation was significantly less and inflammation markers were also lower in group C compared to group B (p<0.05). Histological findings were significant for greater fibrosis, neutrophils' infiltration and neovascularization in group B compared to both group A and C. Regarding mesh cultures, more specimens were tested positive in group B (p <0.05). Outcomes between group A and C did not differ. CONCLUSION: NAC effectively ameliorated adhesion formation and inflammation in a potentially septic environment where a prosthetic mesh was placed.

A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: a Hellenic Cooperative Oncology Group study.

BACKGROUND: Colon cancer is a public health problem worldwide. Adjuvant chemotherapy after surgical resection for stage III colon cancer has been shown to improve both progression-free and overall survival, and is currently recommended as standard therapy. However, its value for patients with stage II disease remains controversial. When this study was designed 5-fluorouracil (5FU) plus leucovorin (LV) was standard adjuvant treatment for colon cancer. Irinotecan (CPT-11) is a topoisomerase I inhibitor with activity in metastatic disease. In this multicenter adjuvant phase III trial, we evaluated the addition of irinotecan to weekly 5FU plus LV in patients with stage II or III colon cancer. METHODS: The study included 873 eligible patients. The treatment consisted of weekly administration of irinotecan 80 mg/m2 intravenously (i.v.), LV 200 mg/m2 and 5FU 450 mg/m2 bolus (Arm A) versus LV 200 mg/m2 and 5FU 500 mg/m2 i.v. bolus (Arm B). In Arm A, treatments were administered weekly for four consecutive weeks, followed by a two-week rest, for a total of six cycles, while in Arm B treatments were administered weekly for six consecutive weeks, followed by a two-week rest, for a total of four cycles. The primary end-point was disease-free survival (DFS) at three years. RESULTS: The probability of overall survival (OS) at three years was 0.88 for patients in Arm A and 0.86 for those in Arm B, while the five-year OS probability was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.436). Furthermore, the probability of DFS at three years was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.334). With the exception of leucopenia and neutropenia, which were higher in patients in Arm A, there were no significant differences in Grades 3 and 4 toxicities between the two regimens. The most frequently recorded Grade 3/4 toxicity was diarrhea in both treatment arms. CONCLUSIONS: Irinotecan added to weekly bolus 5FU plus LV did not result in improvement in disease-free or overall survival in stage II or III colon cancer, but did increase toxicity. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12610000148077.

Cytokeratin 7 and 20 expression in gallbladder carcinoma.

Cytokeratin expression is being frequently used for the differential diagnosis of carcinomas originating from different sites. Among the various cytokeratins, the combination of cytokeratins (CKs) 7 and 20 is considered to be the most useful for this purpose. However, there are very few reports in the literature regarding CK7 and CK20 expression in gallbladder carcinoma (GBC). In this paper we studied the immunohistochemical expression of CK7 and CK20 in 42 GBC cases. In addition, we studied 25 randomly selected cases of lithiasis associated chronic cholecystitis (LaCC) as controls. CK7/CK20 immunoprofile was assessed in relation to tumour differentiation, depth of invasion, and p53 protein expression. Twenty-nine GBC cases (69.05%) were CK7-positive, and 12 cases (28.57%) were CK20-positive. Tumour differentiation was not correlated with CK7 or CK20 immunoreaction. Regarding tumour depth of invasion, the CK7+/CK20- group presented a significant correlation with early stage (T1) disease (p = 0.04). p53 expression was correlated with both CK7 (p = 0.05) and CK20 (p = 0.023) expression. All the cases of LaCC demonstrated diffuse intense CK7 positivity of the mucosal epithelium, while CK20 was only focally positive in 13/25 cases. Our results along with the data from the literature indicate that CK7/CK20 expression may be of clinical significance, and further investigation in this direction is needed.

Dilatation and curettage in endometrial cancer. What is the correlation with hysterectomy histology? A 14 years retrospective cohort study.

PURPOSE: The aim of the present study is to evaluate the concordance between preoperative endometrial sampling histopathology performed by conventional dilatation and curettage (D&C) and final histopathological diagnosis after total hysterectomy concerning tumor grade and subtype in patients with endometrial cancer (EC). METHODS: In this comparative retrospective study, 203 women with endometrial cancer were included who underwent at first dilatation and curettage and then total hysterectomy. The preoperative histopathological report obtained by dilatation and curettage was compared with the final histopathology after total hysterectomy to assess the accuracy of endometrial sampling. RESULTS: Comparison of preoperative with postoperative histopathological results showed an overall 5.9% and 10.9% discordance regarding endometrial cancer histological subtype and grade, respectively. Six (4.9%) of the patients with preoperative grade 1 were grade 2 and 1 (0.8%) was found to be grade 3. Three (8.3%) of the patients with preoperative grade 2 were found to be grade 3 after hysterectomy. Discordance is higher for endometrioid endometrial cancer grade 2 (25%) compared with grade 1 (5.7%) and 3 (18.8%). CONCLUSION: Patients should be informed and consent for the potential discrepancy between the pre and postoperative histopathological features of malignancy. This discrepancy may result in either under or overtreatment. Thus, it should be accounted for when counseling for a major operation.

DNA methylation patterns of RAR-ß2 and RASSF1A gene promoters in FNAB samples from Greek population with benign or malignant breast lesions.

BACKGROUND: Promoter hypermethylation is common in Breast Cancer (BC) with studies mainly in histological specimens showing frequent methylation of tumor suppressor genes (TSGs) compared with normal tissues. The aim of this study was to estimate the frequency of promoter methylation of RAR-ß2 and RASSF1A genes in breast FNAB material aiming to evaluate the methylation status of these two genes as biomarker for detecting BC in Greek population. METHODS: FNAB material from 104 patients was collected for cytological evaluation and epigenetic analysis. DNA was extracted and subjected to bisulfite conversion. A methylation-specific PCR was carried out and the final products were separated with electrophoresis in 2% agarose gels. RESULTS: From 104 samples, RASSF1A hypermethylation was observed in 78 (75%) and RAR-ß2 hypermethylation in 64 (61.6%). 84% and 78% of the cases diagnosed with breast malignancy (n = 50) were methylated for RASSF1A and RAR-ß2, respectively. Methylated RASSF1A and RAR-ß2 were also detected in 88.3% and 76.5% in samples diagnosed as suspicious for malignancy (n = 17) and in 57.2% of samples diagnosed with atypia (n = 14). The Odds Ratio for breast malignancy was 4.545 in patients with RASSF1A hypermethylation and 9.167 in patients with RAR-ß2 hypermethylation underlying their promoter's methylation positive correlation with breast malignancy. CONCLUSION: To optimize the sensitivity and specificity of this epigenetic setting, more TSGs related to BC should be gradually imported in our evaluated methylation panel and be validated in a larger study sample with the aim that the obtained epigenetic profiles will provide clinicians with valuable tools for management of BC patients in Greece.

Mucous cysts of the nose: a postrhinoplasty complication?: a long-term follow-up.

Mucous cysts are very rare complications following rhinoplasty; less than 20 cases have been reported in literature. We present 2 new cases. The first case presented a cyst located beneath the glabella and above the articulation between the spina nasalis and the os nasale. The lesion first appeared 22 months following elective rhinoplasty. The treatment was complete surgical excision using a direct open approach. In the second case, a cyst was indentified between the right inner canthus and the sidewall of the nose. It appeared 6 months following elective rhinoplasty. The treatment was complete surgical excision through a transcartilaginous approach. Both patients had good postoperative results with no evidence of recurrence after a 7- and 8-year follow-up period, respectively. We believe that it is possible to prevent the appearance of mucous cysts after rhinoplasty, with careful dissection and avoidance of dispersion of mucosal material into a subcutaneous plane.

Pyloric and foveolar type metaplasia are important diagnostic features in Crohn's disease that are frequently missed in routine pathology.

Pyloric type metaplasia (PYME) as evidence of chronic mucosal damage, is one of the main histopathological findings for diagnosing Crohn's Disease (CD) in terminal ileum biopsies, according to the latest guidelines but still frequently underdiagnosed in routine pathology. Foveolar metaplasia (FOME) changes in mucosa, another aspect of the chronic post -inflammatory Ulcer Associated Cell Lineage (UACL), have only been reported in a few cases. However, their clinical significance has not been investigated in depth except in pouchitis. The aim of this study was to investigate the importance of meticulous study of terminal ileum biopsies for the recognition of PYME/FOME as an adjunct finding helpful for the diagnosis of CD. In the present study, two experienced gastrointestinal pathologists, have reviewed 105 terminal ileum biopsies from 105 patients with CD, using a protocol of 15 sections on average per biopsy. In 21% (22/105) of cases PYME was recognized and in 4% (4/105) FOME was also present. PYME/FOME had not been detected in 83% of these cases in the original reports. FOME was also identified in terminal ileum biopsies, a feature not reported previously in CD. Conclusively, PYME/FOME can be easily missed in terminal ileum biopsies from patients with suspected or known CD unless a meticulous study of the histologic material is carried out combined with awareness of the pathologist about its importance.

Ossifying fibromyxoid tumor may express CD56 and CD99: a case report.

Ossifying fibromyxoid tumor (OFMT) is an uncommon soft tissue neoplasm characterized by a combination of myxoid and/or fibrous stroma with areas of ossification. Although most authors postulate a neuroectodermal origin for this peculiar tumor, there is no agreement in the literature regarding its histogenesis. In this article, we present the immunohistochemical findings of a case of a 39-year-old white male with an OFMT of the soft tissue in the mandibular region. The tumor was positive to S-100 protein, glial fibrillary acidic protein, CD99, CD56 and negative to smooth muscle actin, cytokeratins AE1/AE3, epithelial membrane antigen, and CD68. To the best of our knowledge, this is the first case reported to be positive to CD56 and CD99. Immunoreactivity to these two antibodies, together with reactivity for S-100 protein and glial fibrillary acidic protein, suggests that OFMT is of a neuroectodermal origin. In our opinion, in the absence of reactivity to at least one neuroectodermal marker one should seriously question a diagnosis of OFMT.

Para-articular extraskeletal chondroma mimicking first metatarsophalangeal synovitis.

Extraskeletal chondroma is a rare benign tumor with symptoms that could mimic other common musculoskeletal pathological entities. We present a rare case of an extraskeletal para-articular chondroma of the first metatarsophalangeal joint which was initially misinterpreted as joint synovitis, based on magnetic resonance imaging findings. Histology revealed benign chondroma of the foot, which was finally treated with radical surgical excision. More than 2 years postoperatively, no recurrence of the tumor has been encountered.

Management of atypical polypoid adenomyomas. A case series.

OBJECTIVE: Atypical polypoid adenomyomas (APAs) are endometrial, non-malignant, focal, and non-invasive lesions that are intriguing for their histological resemblence to invasive endometrioid adenocarcinoma or malignant mixed Müllerian tumor. The aim of this study was to present our clinical experience, regarding the reproductive outcome, the recurrence rate, and the association with hyperplasia and cancer, in a small series of patients with APA. STUDY DESIGN: Retrospective case series of patients treated for APA in a single private hospital setting from 1998 to 2016. All patients underwent diagnostic hysteroscopy and hysteroscopic removal of the lesion. Follow-up was performed annually with endovaginal ultrasonography and hysteroscopy when necessary. RESULTS: Nine patients (mean age: 37.9 years-old ±8.3years) were treated because of menorrhagia, infertility, and incidental asymptomatic endometrial lesions with operative hysteroscopy. Mean follow-up was 10.0 years (±5.8years). Three patients intended for pregnancy and 2 of them had achieved a full term delivery. There were 2 recurrences (22.2%), two cases of atypical endometrial hyperplasia (22.2%), and 2 patients with endometrioid adenocarcinoma (22.2%), all within the first 5 years. CONCLUSIONS: It appears that APAs exhibit a significant recurrence rate and they may be related both to atypical endometrial hyperplasia and endometrial adenocarcinoma; therefore, clinicians should be aware of these lesions in order to individualize treatment according to the patent's age and fertility history.

Immunohistochemical expression pattern of metastasis suppressors KAI1 and KISS1 in endometriosis and normal endometrium.

OBJECTIVE: To analyze the expression pattern of metastasis suppressors KAI1 and KISS1 in the endometrium of patients with and without endometriosis. STUDY DESIGN: In this pilot study, tissue samples were prospectively collected from 38 patients with endometriosis and 29 without endometriosis, undergoing operative laparoscopy in the proliferative phase of the menstrual cycle; diagnosis or absence of endometriosis was confirmed histologically. Protein expression of KAI1 and KISS1 were analyzed immunohistochemically in endometriotic lesions and the eutopic endometrium of patients with endometriosis and without endometriosis. RESULTS: KAI1 expression was significantly decreased in the glandular eutopic endometrium of endometriosis patients as compared with that of patients without endometriosis (p=0.008). On the other hand, in endometriosis patients, KAI1 expression was significantly increased in the ectopic as compared with the eutopic endometrial stroma (p=0.021). There were no other significant differences in KAI1 expression between different groups. KISS1 expression in the ectopic glandular endometrium was significantly increased as compared with the eutopic glandular endometrium from patients with (p=0.004) and without endometriosis (p=0.008). There was no significant difference in KISS1 protein expression in the stromal endometrium between the three groups. CONCLUSIONS: KAI1 and KISS1 are implicated in the pathogenesis and maintenance of endometriosis. Future studies should investigate whether KAI1 and KISS1 could be used as markers for early and minimally invasive detection of endometriosis based on their differential protein expression pattern in the eutopic endometrium of patients with and without endometriosis.