Histological and immunohistochemical characteristic of the gingival stroma in the portion of the third molars in children of various age.

OBJECTIVE: Aim: To evaluate the state of the gingival stromal elements in the portion of the third molars requiring extraction of these teeth due to orthodontic indications considering the stage of tooth germ formation. PATIENTS AND METHODS: Materials and Methods: The surgery to extract third molars due to orthodontic indications was performed on 95 children aged 11 to 18 years. The three groups of observation were isolated according to clinical-radiological signs: І (n=30) - children aged 11-13 years; ІІ (n=35) - children aged 13-16 years, and ІІІ (n=30) - children aged 16-18 years. During surgery, the samples of gums were taken from the adjacent areas for examination. The samples were fixed, dehydrated, paraffinized for further histological processing. Immunohistochemical methods were used according to the protocols supplied by a producer. In particular, by means of immunohistochemical method, Ki-67, CD-34 antigens and vimentin with primary antibodies against them were determined. The primary antibodies were visualized by the polymeric visualization system with diaminobenzidine giving a brown color to the places of location of the antigens examined. The data obtained were statistically processed. RESULTS: Results: The results of the study showed that specific gravity of the vascular bed in the gingival papillary layer of children was the most variable. It ranges from (12,7±0,09) % at the stage of "D" root formation to (54,8±0,17) % at the "H" stage. Lower concentrations of CD-34 antigens and vimentin are found in the endotheliocytes of children aged 13-16 and 16-18 years, compared to the children aged 11-13 years (p<0,05). No changes were found in the specific volume of the blood vessels, CD-34 antigens and vimentin in the reticular gingival layer of children from the groups of observation. CONCLUSION: Conclusions: Therefore, the conducted histological and immunohistochemical study of the connective gingival tissues in the portion of the third molars in children enables to draw a conclusion that in the process of formation of the root of this tooth a number of changes occur in the gingival stroma. They include an increase of the blood flow volume in the papillary gingival layer on the background of a decreased concentration of CD-34 genes and vimentin, a longer stage of development of the third molar root. The specific volume of the islets of neoangiogenesis of the papillary gingival layer is the largest in children aged 13-16 years.

[Histology of fetal lungs at different gestational age]. / Gistologiya legkikh ploda na raznykh srokakh beremennosti.

The lecture is devoted to the morphological characteristics of the maturation of lung tissue structures in the fetal period. Fetal histology of the lungs presents the intrauterine development of lung tissue in four successive stages: pseudoglandular, canalicular, saccular and alveolar, each has specific morphological criteria. The following morphological features are predetermined: the development of alveolar epithelium, the ratio of mesenchyme towards the area in alveolar spaces, the degree of proliferation and location of vessels of the microcirculatory bed towards prealveolar partitions. During the fetal period the alveolar columnar epithelium is flattened and differentiates into alveolocytes type I and II, the area of the mesenchyme gradually decreases and by the birth of a full-term newborn kid it is present mainly in the thickness between the alveolar septa, microcirculation vessels, initially laying deep in the thickness of the mesenchymal tissue, gradually proliferate, approach the pre-alveolar epithelium, channeling it with the formation of alveolar capillary membranes. Air exchange in the lung tissue is mainly provided with two factors: the presence of second-order alveolocytes capable of producing surfactant, and a sufficient formation of alveoli as well. This work summarizes the basics of fetal lung histology with the demonstration of histological preparations of the lungs at different stages of intrauterine development.

[Clinical and morphological aspects of the use of palpebral implants made of noble metals]. / Kliniko-morfologicheskie aspekty primeneniya pal'pebral'nykh implantatov iz blagorodnykh metallov.

Loading of the upper eyelid with palpebral implants made of noble metals is the modern standard of surgical treatment for paralytic lagophthalmos, and is aimed at increasing the mobility of the upper eyelid and normalizing involuntary blinking movements. This review presents the results of morphological studies, including immunohistochemical studies, reflecting the features of biointegration of palpebral implants in uncomplicated and complicated course of the postoperative period, and describes the modern understanding of the causes and immunopathological processes underlying the development of nonspecific inflammatory response, which is one of the most serious complications that often becomes an indication for implant removal.

Superior caval vein syndrome and cardiac inflammatory myofibroblastic tumour in an infant.

The inflammatory myofibroblastic tumour, although very rare, must be considered in the differential diagnosis of intracardiac masses in children as it has systemic implications. We present a case of an infant whose diagnosis was suspected on clinical basis and echocardiogram, but the anatomopathological analysis with immunohistochemical study was essential for the conclusion of the histological type and orientation of the clinical follow-up.

[Difficulties in diagnosis of neuroendocrine tumors of the gastrointestinal tract]. / Trudnosti diagnostiki neiroendokrinnykh opukholei zheludochno-kishechnogo trakta. Klinicheskoe nablyudenie.

We present diagnosis and complex minimally invasive surgical treatment of a patient with long-standing neuroendocrine tumor of the upper gastrointestinal tract. We followed-up a 50-year-old female patient after endoscopic resection of polypoid neoplasm of the stomach for 2 non-organ retroperitoneal neoplasms in the area of hepatogastric ligament. After a comprehensive examination and minimally invasive surgery including laparoscopic resection of retroperitoneal neoplasms, immunohistochemical examination, PET-CT and targeted endoscopic ultrasound of the stomach, we diagnosed a highly differentiated gastric neuroendocrine tumor with metastases into lymph nodes of hepatogastric ligament. Combination of endoscopic and morphological diagnosis with rigorous histological examination of specimen provided correct diagnosis and reasonable strategy of aggressive minimally invasive surgical treatment.

[Pulmonary epithelioid hemangioendothelioma]. / Epitelioidnaya gemangioendotelioma legkikh.

The article describes the clinical, radiological and pathological features of epithelioid hemangioendothelioma (EHE) in 27 adult patients, mainly female. In all cases, with the exception of one, there was a benign course of the disease over many years with a tendency to stabilize growth, the morphological sign of which was the development of widespread sclerotic changes. With the help of immunohistochemical method, the endothelial nature of EHE cells and its relatively low proliferative potential were confirmed. Clinical and morphological features of EHE raise the question of the essence of proliferation of endothelial cells with the formation of tumor-like nodes. There is every reason to consider EHE as a pseudotumor of the type of nodose hyperplasia in the nosological group of dyshormonal hyperplasia, similar to benign leiomyoma of the uterus with lung damage, as we have previously proposed.

Clinicopathological study of annexin A5 & apelin in pre-eclamptic placentae with emphasis on foetal outcome.

Background & objectives: Pre-eclampsia has remained an elusive disease with serious impacts on both maternal and foetal health. Two novel markers, annexin A5 (ANXA5) and apelin are currently of considerable interest. The present study aimed to determine the placental expression of ANXA5 and apelin in pre-eclamptic placentae and also to elucidate if there is any correlation between the expression of these markers and the clinical features of both, mother and neonate. The comparison between gross and histopathological features of pre-eclamptic placentae and controls was another objective. Methods: A prospective, observational study was undertaken for one year. Placentae of pre-eclamptic patients and matched controls (matched for age, ethnic and socio-economic background) were collected along with the clinical data. Gross and histopathological analyses were done and immunohistochemical study of placental sections with ANXA5 and apelin was also undertaken. Results: 79 pre-eclamptic patients and equal numbers of matched controls were included in the study. The difference in weight and dimensions of placentae between the pre-eclampsia group and matched controls was significant. Histopathological features noted in the pre-eclamptic placentae included decidual vasculopathy, infarction, perivillous fibrin deposition, increased syncytial knots and distal villous hypoplasia. There was a significant reduction in the expression of both ANXA5 and apelin in pre-eclamptic placentae compared to controls. Among pre-eclamptic patients, the intensity of ANXA5 and apelin expression showed a significant association with respect to neonatal resuscitation. Furthermore, the intensity of apelin showed expression a significant correlation with the requirement of sick neonatal care unit treatment. Interpretation & conclusions: The results of the present study suggest that both ANXA5 and apelin levels are reduced in pre-eclamptic placentae. Hence, it is recommended to further explore the impact of these markers on pregnancy outcomes by undertaking randomized controlled trials.

Mesonephric-like adenocarcinoma of the ovary in an elderly woman: A case report and a review of the literature.

Mesonephric-like adenocarcinoma (MLA) is a rare tumor that occurs in the uterine endometrium and ovary. It morphologically and immunohistochemically resembles cervical mesonephric adenocarcinoma (MA). Here, we present a case of MLA of the ovary along with a literature review. An asymptomatic 84-year-old woman presented with a pelvic mass, detected by computerized tomography. Magnetic resonance imaging demonstrated a polycystic mass with a solid component in the left adnexal region. The solid component showed low signal intensity on T2-weighted imaging and high signal intensity on diffusion-weighted imaging. We strongly suspected an ovarian malignant tumor; therefore, surgical resection of the uterus and adnexa was performed. Macroscopically, the tumor was predominantly solid with yellowish-tan cut surface. Microscopically, it showed a tubular pattern with intraluminal colloid-like material resembling MA. The tumor cells were negative for estrogen receptor, calretinin, and CD10 and positive for PAX8 and TTF-1. These findings are consistent with those of MLA.

[IgG4-associated sclerosing cholangitis mimicking cholangiocellular carcinoma]. / IgG4-assotsiirovannyi skleroziruyushchii kholangit, protekayushchii pod maskoi kholangiotsellyulyarnoi kartsinomy.

The paper presents an update on the epidemiology, main clinical manifestations, and diagnostic methods in IgG4-associated sclerosing cholangitis. It highlights the importance of morphological and immunohistochemical studies in the diagnosis of the disease. It describes a case of diagnosing IgG4-associated sclerosing cholangitis when examining the surgical material from a patient with suspected cholangiocellular carcinoma of the hepatic hilus.

[Immunohistochemical and molecular diagnosis of inflammatory myofibroblastic tumor of the uterus: a literature review and a clinical case]. / Immunogistokhimicheskaya i molekulyarnaya diagnostika vospalitel'noi miofibroblasticheskoi opukholi matki: klinicheskoe nablyudenie i obzor literatury.

Inflammatory myofibroblastic tumors of the uterus (uIMT) are rare and difficult to diagnose neoplasms, since the morphological characteristics of this tumor are not specific and are found in other pathological changes. In addition, until recently, specific uIMT markers have not been identified and their diagnostic standards not defined. However, in recent years, there have been more and more studies aimed to identify characteristic morphological, immunohistochemical, and molecular genetic features for the differential diagnosis of uIMT. Recent papers studying uIMT indicate anaplastic lymphoma kinase (ALK) as a potentially reliable marker of uIMT. This communication describes a clinical case of uIMT in a 40-year-old woman who has been preoperatively diagnosed with a large subserous interstitial myomatous nodule. The final diagnosis was made, by analysing a combination of morphological and immunohistochemical signs. This clinical case with a literature review is indicated to consider ALK as a key criterion in the diagnosis of uIMT, as well as the relationship between subsequent treatment and the presence of ALK in the studied tissues.

Clinicopathological and survival characteristic of mismatch repair status in ovarian clear cell carcinoma.

BACKGROUND AND OBJECTIVES: We sought to explore the expression of mismatch repair (MMR) status and its correlation with clinicopathologic and survival characteristics in ovarian clear cell carcinoma (OCCC). METHODS: Expression of four MMR proteins (MLH1, PMS, MSH2, and MSH6) were measured using tissue microarray-based immunohistochemistry in 120 OCCC patients. The associations of clinicopathologic parameters with recurrence-free survival (RFS) and overall survival (OS) were analyzed by the Kaplan-Meier method, and multivariate analysis was further performed by the Cox regression model. RESULTS: Overall, 120 OCCC patients met the entry criteria, and their MMR status was detected, consisting of 24 patients with dMMR and 96 patients with proficient MMR (pMMR). Patients with dMMR were strongly associated with platinum-sensitive disease (P = .006) and large tumor volume (P = .038). Among all the patients who have received surgery, tumors with dMMR had a better RFS and OS than those with pMMR (hazard ratio [HR] for recurrence: 0.459 [95% confidence interval {95% CI} = 0.224-0.940], P = .029; HR for death: 0.381 [95% CI = 0.170-0.853], P = .015). In subgroup analysis, dMMR patients experienced a better trend of RFS (HR = 0.273; P = .055) and OS (HR = 0.165; P = .040) than pMMR cases among early stages (I-II), but this difference was not observed in advanced stage (III-IV) patients. Meanwhile, pMMR was associated with a more favorable trend of prognosis than dMMR in platinum-resistant patients (RFS: HR = 0.317, P = .051; OS: HR = 0.370, P = .046). Multivariate analysis revealed that only advanced stages (III-IV) were adverse independent prognosticators for both RFS (HR = 5.938 [95% CI = 2.804-12.574]; P < .001) and OS (HR = 6.209 [95% CI = 2.724-14.156]; P < .001). CONCLUSION: Tumors with dMMR were related to better OS in OCCC on univariate analysis. Only the tumor stage was an independent prognosticator for both RFS and OS. MMR status is a potentially valuable prognostic index in OCCC patients, and larger prospective studies are required to validate its prognostic role.

[Metastatic leiomyoma or synchronous lesion of the uteri corpus and vulva?] / Metastaziruiushchaia leiomioma ili sinkhronnoe porazhenie tela matki i vul'vy?

OBJECTIVE: To reveal the morphological characteristics of simultaneously diagnosed leiomyoma of the corpus uteri and vulva. SUBJECT AND METHODS: The paper describes a case of multiple uterine leiomyomas concurrent with vulvar leiomyoma in a 39-year-old patient with progressive tumor nodule growth over 2 years. Vulvar tumor was biopsied simultaneously with extirpation of the uterus; vulvar leiomyoma was removed six months later. Histological and immunohistochemical studies: such as hematoxylin and eosin staining, the expression of smooth muscle actin, desmin, and progesterone and estrogen receptors, S100, CD10, and determination of Ki-67 proliferation index, were conducted. RESULTS: The largest (14-cm) multiple tumor nodule in the corpus uteri had the structure of leiomyoma of uncertain malignant potential; the large (8-cm) vulvar tumor was a leiomyoma with hyalinosis. The immunohistochemical profile of uterine and vulvar leiomyoma (smooth muscle actin+, desmin+, progesterone+, estrogen+ receptors, CD117-, and Ki-67) was the same (1-3%). The vulvar leiomyoma was assumed to be a tumor of metastatic origin. CONCLUSION: Vulvar leiomyoma is rare; it can arise from smooth muscle tissue of various anatomical structures of the skin and soft tissues. The pathogenesis of the so-called metastatic leiomyoma is unclear; there are concepts of a metaplastic transformation of subcelomic mesenchyme and multifocal smooth muscle proliferation. The presented case demonstrates the synchronous development of uterine and vulvar leiomyoma.

[To the question of proliferative verrucous leukoplakia malignant potential]. / K voprosu o zlokachestvennom potentsiale proliferiruyushchei verrukoznoi leikoplakii.

AIM OF STUDY: To study of neoplastic transformation of the epithelial cells of the oral mucosa with verrucous hyperortokeratosis, verrucous carcinoma and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Oral mucous membrane biopsies of 33 patients with clinical diagnosis of proliferative verrucous leukoplakia were investigated. Histologically in 19 cases (57.6%) was revealed verrucous hyperorthokeratosis, in 8 cases (24.2%) - verrucous carcinoma and in 6 cases (18.2%) - oral squamous cell carcinoma. Tissue antigens were determined using mouse monoclonal antibodies to Ki-67 and mouse monoclonal antibodies to cytokeratin 15. RESULTS OF THE STUDY: In comparison with the proliferative activity of epithelial cells in the malpighian layer in verrucous hyperorthokeratosis (17.2±8.1%) was detected increasingof cell proliferation in epithelial growth zone in verrucous carcinoma (33.8±8.1%) and in peripheral zone of solid areas in oral squamous cell carcinoma (51.2±35.7%). A significant decrease in the expression of cytokeratin 15 in the cytoplasm of tumor cells was noted inverrucous carcinoma and oral squamous cell carcinoma in comparison with verrucous hyperorthokeratosis. CONCLUSION: The obtained results proclaim that there is no stage of epithelial dysplasia during tumor transformation of proliferative verrucous leukoplakia into verrucous carcinoma and oral squamous cell carcinoma. Verrucous carcinoma by the nature of proliferative activity, cell atypia and expression of cytokeratin 15 corresponds to carcinoma in situ.

A giant superinfected uterine angioleiomyoma with distant septic metastases: an extremely rare presentation of a benign process and a systematic review of the literature.

PURPOSE: Uterine angioleiomyoma is a rare type of leiomyoma variant and there are few cases reported in the literature. The definitive diagnosis is usually obtained only after the histopathologic examination because there are no specific imaging criteria for this disease. The objective of this article is to review published cases about this clinical condition. METHODS: We report a case of giant angioleiomyoma superinfected by S. agalactiae with the development of latero-cervical distant metastasis in a premenopausal woman. Firstly, the case herein reported was orientated as an endometrial stroma sarcoma in the peri-operative histologic examination by frozen sections. It was treated with laparotomic total hysterectomy, bilateral salpingo-oophorectomy, inframesocolic omentectomy and pelvic and paraaortic lymph node dissection. Postoperative definitive anatomopathological analyses using a proper immunohistochemical panel revealed a case of uterine angioleiomyoma. We also review other case reports published about this clinical condition. RESULTS: We present the first case reported in the literature, in our knowledge, of a giant angioleiomyoma superinfected by S. agalactiae with the development of distant septic metastases. Immunohistochemistry permitted the definitive diagnosis of angioleiomyoma. Treatments previously reported are hysterectomy or tumor resection and any patient recurred. CONCLUSIONS: The definitive diagnosis is usually obtained after the definitive histopathologic examination since the use of immunohistochemical study has an important role in this regard. Complete surgical removal of the lesion is the treatment of choice, with no recurrent cases reported to date.

[Angiogenesis-related factors in the placenta of pregnant women with congenital heart diseases]. / Faktory angiogeneza v platsente beremennykh s vrozhdennymi porokami serdtsa.

OBJECTIVE: To study the features of angiogenesis of the placental villous chorion in women whose gestation took place in congenital heart disease (CHD). MATERIAL AND METHODS: Thirty-five placentas obtained from women with full-term pregnancy, including 20 cases of non-operated CHD and 15 as a result of physiological pregnancy and childbirth (a control group), were studied. A placental morphological examination was made according to the standard scheme using routine stains and immunohistochemical techniques involving reactions with mouse monoclonal antibodies against VEGF, CD34, and SMA. RESULTS: The placentas of women with CHD showed a set of pathological changes, including impaired chorionic villous maturation and marked dystrophic and necrobiotic changes, the latter being more common in the placental marginal zones. Placental VEGF expression in women with CHD was significantly higher than that in the controls, especially at the edge of the placental disc. On the contrary, CD34 expression in all placental sections was lower in CHD. The distribution of SMA in the myofibroblasts of chorionic villous vessels in CHD was characterized by diffuse growth of actin expression. The specific volume of the cell surface with a positive reaction to actin significantly increased in the center, especially in the peripheral zone. CONCLUSION: Thus, the analysis of the studies could establish that hemodynamic disturbance during gestation complicated by CHD was accompanied by remodeling of the villous chorion. Pathological changes in the placental barrier complicate metabolism and gas exchange in the fetoplacental complex. Microvascular remodeling is an important mechanism of placental adaptation to circulatory hypoxic conditions in the presence of CHD and a prerequisite for successful pregnancy termination and childbirth in disease.

[Immunohistochemical study of Ki-67, PHH3, and CK15 protein expression in oral epithelial malignancy]. / Immunogistokhimicheskoe issledovanie ékspressii belkov Ki-67, PHH3 i CK15 pri malignizatsii épiteliia slizistoi obolochki rta.

OBJECTIVE: To investigate the expression of Ki-67, phosphohistone H-3 (PHH3), and cytokeratin 15 (CK15) proteins in the cells of the oral mucosa (OM) according to the degree of its malignant transformation. MATERIAL AND METHODS: OM biopsy specimens from 69 patients diagnosed with focal epithelial hyperplasia, intraepithelial squamous cell neoplasia, cancer in situ, and squamous cell carcinoma were examined. Tissue antigens were determined using mouse Ki-67 monoclonal antibodies, rabbit PHH3 polyclonal antibodies, and mouse CK15 monoclonal antibodies. RESULTS: There was an increase in epithelial proliferative and mitotic activities in squamous cell carcinoma and a sharp decrease in the expression of CK15 in the cytoplasm in cancer in situ and squamous cell carcinoma of the OM. CONCLUSION: The protein CK15 can be used for the differential diagnosis between high-grade dysplasia and OM epithelial malignancy at the stage of carcinoma in situ and squamous cell carcinoma.

[The nasal mucosa and outcomes of dacryocystorhinostomy]. / Sostoianie slizistoi obolochki polosti nosa i rezul'taty dakriotsistorinostomii.

OBJECTIVE: To investigate the impact of the nasal mucosa on the outcomes of dacryocystorhinostomy on the basis of morphologic findings. MATERIAL AND METHODS: The investigation enrolled 73 patients who had undergone endonasal endoscopic dacryocystorhinostomy. Nasal mucosal biopsies were intraoperatively taken from all the patients. The obtained samples were subjected to standard histological examination, as well as to immunohistochemical study using an anti-alpha-smooth muscle actin antibody. To determine the intensity of inflammation in the tissue sample, a chronic inflammation score was calculated. The cell elements positively stained with α-smooth muscle actin were estimated using a semi-automatic method. The patients were divided into groups in accordance with the outcome of surgical treatment after 6 months. RESULTS: An unfavorable outcome of dacryocystorhinostomy was observed in 10 (13.7%) patients. The samples obtained from the patients showed a higher chronic inflammation score (8.33%) and a larger number of the cell elements positively stained with α-smooth muscle actin (6026.38±1944.29). The correlation between the outcome of surgical intervention and the quantitative characteristics of myofibroblasts was statistically significant (p<0.05). CONCLUSION: These studies suggest that there is a direct correlation of the efficiency of endonasal endoscopic dacryocystorhinostomy with the presence and degree of chronic nasal mucosal inflammation at baseline.

[Histological study of urethral plate: a search of the best material for surgical treatment of hypospadias in children].

AIM: to study the microstructure of the urethral plate in patients with a proximal form of hypospadias to justify the use of tissues from the ventral penile surface when creating an artificial urethra. MATERIALS AND METHODS: A histological study of surgical specimens from 10 patients with proximal hypospadias was carried out. The urethral plate, a strip of tissue from the ectopic external urethral orifice located in the penoscrotal angle, to the coronary sulcus, was completely excised and processed by various techniques. A staining with hematoxylin and eosin, picrofuchsin according to Van Gieson, as well as immunohistochemical typing of CD 34, collagen (type I, III, and IV), fibronectin, and smooth myocytes using alpha-smooth muscle actin was performed. RESULTS: All elements which are present in a healthy urethra, such as epithelial cells, blood vessels, normal collagen fibers, smooth muscle cells and complexes of glands, were found in the microstructure of the urethral plate. CONCLUSION: The cytoarchitectonic features of the ventral penile tissues are similar to the microstructure of the healthy urethra, which provides a rationale to consider the urethral plate as a material with optimal bioresistant properties for urethroplasty.

Summary of expression of SPARC protein in cutaneous vascular neoplasms and mimickers.

BACKGROUND: Serum protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein, which regulates cell proliferation and facilitates intracellular transport of albumin bound particles including chemotherapeutic agents such as Nab-paclitaxel/ABI-007. Therefore the presence of SPARC may achieve higher intra-tumoral drug concentration with lower dosage and thus reduce systemic side-effects. Several trials of ABI-007, in melanoma, show promising clinical activity. DESIGN: Fifty-four cases of dermal based neoplasms were retrieved including 24 angiosarcomas (AS), 10 hemangiomas, 9 nodular melanomas, 4 Kaposi sarcomas (KS), 3 leiomyosarcomas (LMS), 3 atypical fibroxanthomas (AFX) and 1 spindle cell squamous cell carcinoma (SSCC). SPARC immunohistochemistry (IHC) was performed with a mouse monoclonal antibody. RESULTS: SPARC expression was detected in a majority of AS (17/24), melanomas (8/9), AFX (3/3), LMS (3/3) and KS (4/4) with some expression in hemangiomas (3/10), while being negative in SSCC (0/1); and was significantly associated with tumor group (p = 0.017). Although a significant difference in overall survival was observed between SPARC expression groups (positive vs. negative) for all patients, there was no significant difference noted among angiosarcoma patients. CONCLUSION: We have confirmed the presence of SPARC expression in melanoma, KS, LMS and AS and also detected it for the first time in AFX. Since paclitaxel has shown some effectiveness in AS, melanoma and KS, ABI-007 could also be beneficial in these patients.

Prevalence and prognostic role of mismatch repair gene defect in endometrial cancer patients.

The study was to evaluate the prevalence of mismatch repair gene defect among Thai patients with endometrial cancer and its association with clinico-pathological features and survivals. The formalin fixed paraffin-embedded blocks of EMC tissue from hysterectomy specimens of patients having surgery in our institution between 1 Jan 1995 and 31 December 2016 were assessed for the immunohistochemical expression of 4 mismatch repair proteins (MLH1, PMS, MSH2, MSH 6). Mismatch repair gene defect was determined by a negative expression of at least 1 protein. Among 385 EMC patients included in the study, mean age was 57.3 ± 10.8 years with 62.3% aged ⩽ 60 years. The most frequent mismatch repair gene defect was MSH6 (38.7%), followed by PMS2 (34.3%), MLH1 (33.2%), and MSH2 (16.4%). Overall, 55.1% showed negative expression of at least one protein. We found significantly higher mismatch repair gene defect in patients aged ⩽ 60 years, with early stage disease, and negative lymph node status than the other comparative groups: 59.2% vs 48.3% for age (p = 0.037), 58.2% vs 45.2% (p = 0.027) for stage, and 58.1% vs 44.6% (p = 0.048) for nodal status. The 5-year progression-free survival, overall survival, and endometrial cancer-specific survival of patients with mismatch repair gene defect was higher than those without gene defect. The differences were statistically significant for only progression-free survival and endometrial cancer-specific survival: 87.7% (95% confidence interval = 83.0%-92.4%) vs 81.5% (95% confidence interval = 75.4%-87.6%) (p = 0.049) for progression-free survival and 91.0% (95% confidence interval = 86.9%-95.1%) vs 85.5% (95% confidence interval = 80.0%-91.0%) (p = 0.044) for endometrial cancer-specific survival, respectively. In conclusion, more than half of Thai endometrial cancer patients had mismatch repair gene defect. The patients with mismatch repair gene defect had significantly younger age (⩽ 60 years) and better prognosis in terms of early stage, negative nodal status, and longer survivals.