Isolated morular squamous metaplasia in endometrial biopsies and curettings: is there a role for repeated sampling?

Squamous morular metaplasia is closely associated with endometrioid proliferative lesions such as endometrial intraepithelial neoplasia, whereas endometrioid adenocarcinoma may also demonstrate squamous differentiation (morular or nonmorular). Alpha-methylacyl-CoA racemase (AMACR; P504s) is an immunohistochemistry marker expressed in many tumors, including prostate adenocarcinoma, renal cell carcinoma, and in a subset of gynecologic carcinomas, predominantly of clear cell histology. In small biopsy samples, the distinction between cervical high-grade squamous intraepithelial lesions (HSILs) involving endocervical glands from endometrioid squamous proliferations can be challenging, given their anatomic vicinity and some degree of morphologic overlap. Following the observation of AMACR positivity by immunohistochemistry within squamous morules in an index case, 35 endometrial samples containing squamous morular metaplasia (25) and nonmorular squamous metaplasia (10), and 32 cases of cervical HSIL involving endocervical glands were stained with AMACR. The endometrial cohort consisted of 2 benign anovulatory endometrium, 7 endometrial polyps, 7 endometrial intraepithelial neoplasia, 4 atypical polypoid adenomyomas, and 15 endometrioid adenocarcinomas. Positive cases were scored as diffuse (≥50%) or focal (<50%). AMACR staining was present in 96.7% of endometrial squamous lesions, including 14 (93.3%) of endometrioid carcinomas, and in all cases of endometrial intraepithelial neoplasia, endometrial polyps, atypical polypoid adenomyomas, and anovulatory endometrium with squamous morular metaplasia or nonmorular squamous metaplasia. In comparison, only 2 cases (5.8%) of cervical HSIL demonstrated positivity for AMACR. In conclusion, AMACR can reliably differentiate the cervical versus endometrial origin of squamous lesions in small biopsy specimens.

Atypical polypoid adenomyoma (APA) is a rare and benign endometrial polypoid lesion typically found in fertile age [1]. Atypical polypoid adenomyoma (APAM) is an uncommon uterine lesion composed of complex endometrioid glands with frequent squamous morular metaplasia and fibromuscular stroma [2]. Atypical Polypoid Adenomyoma was found on histopathological examination of endometrial tissue with polyp in a woman with abnormal uterine bleeding.&nbsp; Atypical Polypoid Adenomyoma as it is uncommon we present this case report. A 38 year old woman who presented with excessive vaginal bleeding with endometrial polyp underwent dilation and curettage and the histopathological examination of the endometrial polyp was consistent with ‘Atypical Polypoid Adenomyoma’ with extensive morular metaplasia.&nbsp; Immunohistochemical marker CD10 was done to establish the diagnosis of morular metaplasia. Patient subsequently underwent total abdominal hysterectomy. Among young nullipara women, conservative treatment is proposed despite the high recurrence rate and the association with endometrial cancer [1].

Levonorgestrel-releasing intrauterine system (LNG-IUS) as an effective treatment option for endometrial hyperplasia: a 15-year follow-up study

Atypical polypoid adenomyoma (APAM) is an uncommon uterine lesion composed of complex endometrioid glands with frequent squamous morular metaplasia and fibromuscular stroma. On endometrial curettage, biopsy or polypectomy specimens, the admixture of endometrioid glands and smooth muscle raises the differential diagnosis of myoinvasive endometrioid carcinoma. Reproductive-age APAM patients may opt for fertility preservation, whereas myoinvasive carcinoma is treated surgically. One previous study reported an incidental finding that the stroma of APAM, in contrast to that of other polypoid lesions, was SATB2-positive. APAM has also been reported to show increased stromal p16 staining. We aimed to assess whether SATB2 and p16 are useful stains for the distinction of APAM from myoinvasive carcinoma and benign adenomyomatous polyps. Cases of 'atypical polypoid adenomyoma' (n=32), 'adenomyomatous polyp' (n=39) and 'myoinvasive endometrioid carcinoma' (n=30) were identified. Morphological features were assessed, along with the intensity and extent of SATB2 and p16 staining in the stromal component of each lesion. SATB2 expression was seen in the stromal components of 30 of 32 (94%) APAMs, versus none of 39 (0%) benign adenomyomatous polyps and five of 30 (17%) myoinvasive endometrioid carcinomas. Stromal p16 expression was seen in 31 of 31 (100%) APAMs, versus 20 of 39 (51%) benign adenomyomatous polyps and 12 of 30 (40%) myoinvasive endometrioid carcinomas. Patchy to diffuse SATB2 and block-type p16 staining of fibromuscular stroma separating atypical endometrioid glands is more consistent with APAM than with myoinvasive endometrioid carcinoma. These stains are potentially useful adjuncts to careful morphological evaluation of endometrial biopsies/curettings.

Atypical endometrial hyperplasia shares genomic abnormalities with endometrioid carcinoma by comparative genomic hybridization

Background: Particularly interesting new cysteine-histidine rich protein (PINCH), as an adapter protein of the LIM family for signal transduction in the integrin and growth factor pathway, is upregulated in the stroma of several common types of cancers and involved in promoting tumor progression. In the present study, we examined PINCH expression in normal endometrium, atypical endometrial hyperplasia and endometrioid carcinoma, and further studied the relationships of PINCH expression with clinicopathological variables in cancer patients. Methods: PINCH expression was examined by immunohistochemistry in 23 normal endometrial samples, 18 atypical endometrial hyperplasias and 48 endometrioid endometrial carcinomas. Results: The PINCH expression in the stroma of cancer (71%) was significantly increased compared to either normal endometrium (17%, p < 0.0001) or atypical hyperplasia (39%, p = 0.017), along with 9 cancers that had stronger PINCH expressions at the invasive margin of the cancers compared to the inner cancers. PINCH expression in cancer was higher in the patients with hypertension (p = 0.041) and estrogen exposure time >30 years (p = 0.021). On the other hand, PINCH expression was not related to menopausal status, gravid status, blood sugar/lipid, family background of cancer, histological grade, myometrial invasion, cervical involvement, lymph nodal metastases, growth pattern, estrogen and progestogen receptors (p > 0.05). Conclusion: The results suggest that PINCH seems to play a role, presently unknown, in the tumorigenesis and development of endometrial cancer that merits further study.

L’expression immunohistochimique de l’antigène PTEN : Un nouvel outil diagnostique dans les néoplasies débutantes de l’endomètre

Atypical polypoid adenomyoma (APA) is a rare and benign endometrial polypoid lesion. APA was found in a 38-year-old woman who presented with excessive vaginal bleeding. Histopathological examination of the polyp was consistent with “APA” with extensive morular metaplasia. Immunohistochemical marker CD10 was done to establish the diagnosis of morular metaplasia. Morular metaplasia is dissimilar to squamous metaplasia. It is sometimes misreported as adenosquamous carcinoma. This case illustrates the significance of morular metaplasia as a differential diagnosis.

BackgroundEndometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear.ObjectivesTo conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding.Search strategySearch of PubMed, Embase and the Cochrane Library from database inception to August 2015.Selection criteriaStudies reporting rates of endometrial cancer and/or atypical hyperplasia in women with premenopausal abnormal uterine bleeding.Data collection and analysisData were independently extracted by two reviewers and cross‐checked. For each outcome, the risk and a 95% CI were estimated using logistic regression with robust standard errors to account for clustering by study.Main resultsSixty‐five articles contributed to the analysis. Risk of endometrial cancer was 0.33% (95% CI 0.23–0.48%, n = 29 059; 97 cases) and risk of endometrial cancer or atypical hyperplasia was 1.31% (95% CI 0.96–1.80, n = 15 772; 207 cases). Risk of endometrial cancer was lower in women with heavy menstrual bleeding (HMB) (0.11%, 95% CI 0.04–0.32%, n = 8352; 9 cases) compared with inter‐menstrual bleeding (IMB) (0.52%, 95% CI 0.23–1.16%, n = 3109; 14 cases). Of five studies reporting the rate of atypical hyperplasia in women with HMB, none identified any cases.ConclusionsThe risk of endometrial cancer or atypical hyperplasia in premenopausal women with abnormal uterine bleeding is low. Premenopausal women with abnormal uterine bleeding should first undergo conventional medical management. Where this fails, the presence of IMB and older age may be indicators for further investigation. Further research into the risks associated with age and the cumulative risk of co‐morbidities is needed.Tweetable abstractContrary to practice, premenopausal women with heavy periods or inter‐menstrual bleeding rarely require biopsy.

Objective: To provide a reference for the diagnosis and treatment of atypical polypoid adenomyoma (APA). Methods: This was a retrospective study of 203 APA patients from 2011 to 2021. The clinicopathological characteristics, treatments, and prognosis were analyzed. Results: The average age at diagnosis of APA patients was 39.30 ± 11.01 years, and premenopausal women accounted for 81.3%. Abnormal uterine bleeding or menorrhagia were the most common clinical manifestations of APA. The uterine fundus (78.3%), followed by the lower segment of the uterus (11.8%), was the most common location of the APA lesions. Abnormal blood vessels were seen on the surface of 28 APA tumors. APA can coexist with atypical endometrial hyperplasia (18.2%) and endometrial cancer (10.8%). Immunohistochemical analysis was performed on 99 samples. In the glandular component, ER (94.8%), PR (94.8%), Ki-67 (51.5%), p53 (45.6%), PTEN (18.8%), and mismatch repair proteins (96.4%) were positively expressed. Stromal immunophenotype expression was exhibited as follows: CD10-(89.5%), p16+(86.9%), h-caldesmon-(66.7%), Desmin+(75%), and Vimentin+(88.9%). Fifty-five APA patients received TCR, and 33 of them received adjuvant therapy after the operation. The postoperative recurrence rate (9.1% vs. 36.4%, p < 0.05) and malignant transformation rate (3.0% vs. 18.2%, p < 0.05) of the treated group were significantly lower than the untreated group. Conclusions: APA usually occurs in women of childbearing age, and the diagnosis is based on pathological morphology. APA has a low malignant potential, and those who have fertility requirements can undergo conservative TCR treatment, supplemented by progesterone treatment after surgery and close follow-up. Total hysterectomy is the treatment of choice for APA patients with atypical endometrial hyperplasia around the lesion.

ARID1A Regulates Progesterone Receptor Expression in Early Endometrial Endometrioid Carcinoma Pathogenesis

The upper two-thirds of the uterus above the level of the internal cervical os is called the corpus. The fallopian tubes enter at the upper lateral corners of a pear-shaped body. The portion of the muscular organ that is above a line joining the tubo-uterine orifices is often referred to as the fundus. The major lymphatic trunks are the utero-ovarian (infundibulopelvic), parametrial, and presacral, which drain into the hypogastric, external iliac, common iliac, presacral, and para-aortic nodes. Although a direct route of lymphatic spread from the corpus uteri to the para-aortic nodes through the infundibulopelvic ligament has been suggested from anatomical and sentinel lymph node studies, direct metastases to the para-aortic lymph nodes are uncommon. The vagina and lungs are the common metastatic sites. The FIGO Committee on Gynecologic Oncology, following its meeting in 1988, recommended that endometrial cancer be surgically staged. There should be histologic verification of grading and extent of the tumor. All tumors are to be microscopically verified. Endometrioid carcinoma: adenocarcinoma; adenoacanthoma (adenocarcinoma with squamous metaplasia); and adenosquamous carcinoma (mixed adenocarcinoma and squamous cell carcinoma). Mucinous adenocarcinoma. Serous adenocarcinoma. Clear cell adenocarcinoma. Undifferentiated carcinoma. Mixed carcinoma (carcinoma composed of more than one type, with at least 10% of each component). Type 1 (grade 1 and 2 endometrioid carcinoma) may arise from complex atypical hyperplasia and is linked to unopposed estrogenic stimulation. Type 2 includes grade 3 endometrioid tumors as well as tumors of non-endometrioid histology and develops from atrophic endometrium. GX: Grade cannot be assessed. G1: Well differentiated. G2: Moderately differentiated. G3: Poorly or undifferentiated. G1: less than 5% of a nonsquamous or nonmorular solid growth pattern. G2: 6%–50% of a nonsquamous or nonmorular solid growth pattern. G3: greater than 50% of a nonsquamous or nonmorular solid growth pattern. Notable nuclear atypia (pleomorphism and prominent nucleoli), inappropriate for the architectural grade, raises the grade of a grade 1 or grade 2 tumor by 1. In serous and clear cell adenocarcinomas, nuclear grading takes precedent. Most authors consider serous and clear cell carcinomas high grade by definition. Adenocarcinomas with squamous differentiation are graded according to the nuclear grade of the glandular component. The current FIGO staging classification for cancer of the corpus uteri is given in Table 1. Comparison of the stage groupings with the TNM classification is given in Table 2. NX: Regional lymph nodes cannot be assessed. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis to pelvic lymph nodes. N2: Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes. MX: Distant metastasis cannot be assessed. M0: No distant metastasis. M1: Distant metastasis (includes metastasis to inguinal lymph nodes or intraperitoneal disease). Corpus cancer is surgically staged, therefore procedures previously used for determination of stage are no longer applicable (e.g. the findings of fractional curettage to differentiate between Stage I and Stage II). There may be a small number of patients with corpus cancer who will be treated primarily with radiation therapy. In these cases, the clinical staging adopted by FIGO in 1971 would still apply, but designation of that staging system should be noted. Ideally, distance from tumor to serosa should be measured. The presence of lymphovascular space invasion (LVSI) should also be reported in the pathological report of the hysterectomy specimen. A LVSI-positive status has a significantly worse prognosis, especially if extensive LVSI is found [1]. The distinction by LVSI status could be more relevant than the distinction between Stages IA and IB for predicting survival in Stage I endometrial cancer [2]. As a minimum, any enlarged or suspicious lymph nodes should be removed in all patients. For high-risk patients (grade 3, deep myometrial invasion, cervical extension, serous or clear cell histology), complete pelvic lymphadenectomy and resection of any enlarged para-aortic nodes is recommended. Worldwide, endometrial cancer is the sixth most common malignant disorder with approximately 290 000 new cases annually. The incidence is higher in high-income countries (5.5%) compared with low-income countries (4.2%), although specific mortality is higher in the latter. The cumulative risk of endometrial cancer up to the age of 75 years has been estimated as 1.6% for high-income regions and 0.7% for low-income countries [3]. This difference has been associated with an epidemic of obesity and physical inactivity, two important risk factors, in high-income countries. Moreover, endometrial cancer patients with obesity also tend to have a poorer outcome [4]. On the other hand, physical activity and long-term use of continuous combined estrogen–progestin therapy is associated with a reduced risk of endometrial cancer [4,5]. Obesity is associated with earlier age at diagnosis, and with endometrioid-type endometrial cancers. Similar associations were not observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis [6]. In North America and Europe, endometrial cancer is the most frequent cancer of the female genital tract and the fourth most common site after breast, lung, and colorectal cancer [3]. The incidence is rising as life expectancy increases. Furthermore, an estimated 23 700 European women died of endometrial cancer in 2012, which is the eighth most common cause of death from cancer in women [7]. Importantly, the corrected corpus uteri cancer mortality rates showed a decrease in most European Union member states among women born before 1940 [8]. In North America, it is the seventh most frequent cause of death, with approximately 55 000 new cases and 10 000 estimated new deaths each year [3]. The increase in endometrial cancer incidence rates after 2002 may be related to the widespread decrease in estrogen plus progestin menopausal hormone therapy use, which has been reported to lower endometrial cancer risk in overweight and obese women [9]. However, the main reasons underlying the increase in endometrial cancer incidence in high-income countries remain the increasing prevalence of obesity in postmenopausal as well as the increased life expectancy. Endometrioid adenocarcinoma progresses through a premalignant phase of intraepithelial endometrial neoplasia in a large proportion of cases [10]. Other forms such as serous and clear cell carcinoma arise as a result of a sequence of genetic mutations. In serous endometrial cancer, the mutant p53 plays a pivotal role [11]. Endometrial cancer research has gained some momentum in recent years and now provides better information for clinical practice. Its early presentation following postmenopausal bleeding results in a generally good prognosis, but it should be treated using evidence-based protocols, and where appropriate, by expert multidisciplinary teams. The role of population screening for endometrial cancer remains low [12], although certain high-risk groups such as those with Lynch type 2 syndrome can undergo endometrial surveillance by biopsy, or transvaginal ultrasonography if post menopausal. Transvaginal ultrasound is reasonably sensitive and specific but screening of asymptomatic women has in general been recommended only for those with Lynch syndrome [13]. Following presentation, ultrasound is an effective first test with a high negative predictive value when the endometrial thickness is less than 5 mm. In one of the largest studies undertaken, there was a negative predictive value of 96% among 1168 women in whom the results of transvaginal ultrasound were correlated with an endometrial biopsy obtained by curettage [14]. When a biopsy is required, this can be obtained usually as an office procedure using a number of disposable instruments developed for this purpose. In certain cases, hysteroscopy may be helpful, and with flexible instruments can also be done without recourse to general anesthesia. However, the biological role of cells that are transtubally flushed during hysteroscopy remains uncertain. If cervical stenosis or patient tolerance does not permit an office procedure, hysteroscopy and curettage under anesthesia may be necessary. Individuals whose pelvic examination is unsatisfactory may also be evaluated with transvaginal or abdominal ultrasound to rule out concomitant adnexal pathology. Following a histopathologic diagnosis of endometrial adenocarcinoma, the local extent of the tumor, and evidence of metastatic disease should be determined. In addition, the perioperative risk should be assessed. As a minimum, the pathology report from endometrial sampling should indicate the tumor type and grade of the lesion. A chest X-ray, full biochemistry (renal and liver function tests), and blood count are routine. A serum CA125 may be of value in advanced disease for follow-up. Evaluation for metastasis is indicated particularly in patients with abnormal liver function tests, and clinical findings such as parametrial or vaginal tumor extension. In high-risk patients, imaging of the abdomen and lymph nodes may help determine the surgical approach. In certain situations, cystoscopy and/or proctoscopy/barium enema may be helpful if direct extension to the bladder or rectum is suspected. Tumor grade 3 (poorly differentiated). More than 50% of myometrial invasion. Lymphovascular space invasion. Non-endometrioid histology (serous, clear cell, undifferentiated, small cell, anaplastic, etc.). Cervical stromal involvement. The most accurate means of assessing both depth of myometrial invasion and cervical involvement is MRI scanning and intraoperative frozen section [15–17]. CT and MRI are equivalent in terms of evaluating nodal metastases, but neither is good enough to replace surgical lymph node assessment, which provides histological confirmation [18,19]. The role of PET-CT and PET-MRI is currently being investigated. Nonsurgical staging for endometrial cancer, where extrauterine disease exists, is inherently inaccurate, particularly in respect to small nodal involvement, intraperitoneal implants, and adnexal metastasis. In 1988, the FIGO Cancer Committee changed the official FIGO staging from clinical to surgical for endometrial cancer. Since that recommendation, considerable debate has ensued as to what constitutes an internationally acceptable approach. A generally recommended protocol would be that the abdomen should be opened with a vertical midline abdominal incision and peritoneal washings taken immediately from the pelvis and abdomen, followed by careful exploration of the intra-abdominal contents. The omentum, liver, peritoneal cul-de-sac, and adnexal surfaces should be examined and palpated for any possible metastases, followed by careful palpation for suspicious or enlarged nodes in the aortic and pelvic areas. The standard surgical procedure should be an extrafascial total hysterectomy with bilateral salpingo-oophorectomy. Adnexal removal is recommended even if the tubes and ovaries appear normal, as they may contain micrometastases. Vaginal cuff removal is not necessary, nor is there any benefit from excising parametrial tissue in the usual case. Where obvious cervical stromal involvement is demonstrated preoperatively, a modified radical hysterectomy has been historically performed. However, there is consensus (ESMO-ESGO-ESTRO) that simple hysterectomy with free-margins together with pelvic lymphadenectomy can be sufficient. There has also been considerable debate on the safety of endoscopic surgery for the treatment of endometrial cancer. Recent studies have demonstrated that laparoscopic removal of the uterus and adnexae (in experienced hands) appears to be safe. Whereas there is no difference in terms of major complications between abdominal hysterectomy and laparoscopically assisted vaginal hysterectomy (LAVH) or total laparoscopic hysterectomy (TLH), the laparoscopic approach is associated with a significantly decreased risk of major surgical adverse event, a shorter hospital stay, less pain, and quicker resumption of daily activities [20–22]. Since the oncological safety of the laparoscopic approach has now been demonstrated in several randomized studies [23,24], hysterectomy and bilateral salpingo-oophorectomy should be performed with laparoscopy in those patients with no contraindications to laparoscopy (e.g. large-volume uterus). This approach can be accompanied by a laparoscopic lymphadenectomy, if surgical staging is to be undertaken. Robotic surgery for the surgical management of the morbidly obese patient is an option only in experienced hands. In such cases, the surgical management using robotics has been reported to be safe and have less perioperative complications compared with open surgery [25]. Retrospective studies have suggested equivalent oncologic outcomes compared with traditional laparoscopic surgery [26,27]. Although mandated through the staging system, lymphadenectomy of the pelvic and para-aortic areas remains controversial. Selective node sampling is of dubious value as a routine and complete lymphadenectomy should be reserved for cases with high-risk features. Many individuals with endometrial cancer are obese or elderly, with other medical problems, and clinical judgment is required to determine if additional surgery is warranted. Any deeply invasive tumor or radiological suggestion of positive nodes is an indication for retroperitoneal lymph node evaluation, with removal of any enlarged or suspicious nodes. Documentation of positive nodes identifies a high-risk population and helps to tailor adjuvant treatment, since patients with Stage III disease appear to benefit from chemotherapy [28]. Indications for aortic node sampling would include suspicious aortic or common iliac nodes, grossly positive adnexae, grossly positive pelvic nodes, and high-grade tumors showing full thickness myometrial invasion. Patients with clear cell, papillary serous, or carcinosarcoma histologic subtypes are also candidates for aortic node sampling. Low-risk tumors will have positive nodes in less than 5% of cases (well differentiated and < 1/2 myometrial invasion) and do not require full surgical staging. These women can be safely operated on by a general gynecologist, but those at greater risk of extrauterine disease, who may require lymphadenectomy, should be referred to a gynecological oncologist since care provided by gynecologic oncologists has been associated with better survival in high-risk cancers [29]. Moreover, primary management by gynecologic oncologists has been suggested to result in an efficient use of health care resources and minimization of the potential morbidity associated with adjuvant radiation [30]. This triaging of women can be done most effectively by a thorough preoperative assessment, paying particular attention to the pathology and to radiological features. Triaging for lymphadenectomy is also possible during surgery. Intraoperative assessment mainly involves assessment of myometrial invasion [15,17,27]. Grading on frozen section is possible, though suboptimal compared with preoperative grading [17]. The effect of waiting time for surgical staging on survival outcome of endometrial cancer is controversial. A recent population-based study concluded that a longer waiting time for surgical staging was associated with worse survival outcomes in uterine cancer [31]. However, when focusing on type I endometrial cancer only, the waiting time for surgical staging was not associated with decreased survival outcome, presumably due to its excellent prognosis anyway [32]. Although required for accurate staging, a therapeutic benefit for lymphadenectomy is controversial. Historically, one case–control study suggested that it may be therapeutic [33] and another showed a good prognosis even in node-positive women [34]. Another retrospective study showed a survival benefit of complete lymphadenectomy for patients with grade 3 tumors [35]. In the UK, the MRC ASTEC trial, however, which randomized 1400 women undergoing surgery for presumed Stage I endometrial cancer to pelvic lymphadenectomy or no lymphadenectomy, showed no therapeutic benefit [36]. An Italian randomized trial of pelvic (and in 30% para-aortic) lymphadenectomy versus no lymphadenectomy in 540 women also did not show any difference in rates of relapse or survival [37]. Both studies have been criticized because of a limited effort with respect to the extent of dissection and lymph node evaluation, because of the high proportion of low-risk patients, and because no direct decision on adjuvant therapy based on lymphadenectomy was part of the protocols. Lymphadenectomy is primarily used for staging and should be considered in women with high-risk factors [38]. Although a direct survival benefit of lymphadenectomy has not been documented, the procedure identifies node-positive patients that may benefit from adjuvant treatment. An international trial of the role of lymphadenectomy to direct adjuvant therapy for high-risk endometrial cancer (STATEC) is planned. The ongoing ENGOT-EN2-DGCG/EORCT 55102 trial aims to answer this question by comparing survival in patients with Stage I grade 3 endometrioid endometrial cancer, Stage I and II type 2 endometrial cancer or Stage II endometrioid endometrial cancer and without metastatic node after randomization for adjuvant chemotherapy. In a retrospective study, para-aortic lymphadenectomy resulted in an improved outcome in intermediate and high-risk patients when compared with pelvic lymphadenectomy alone [39]. However, adjuvant therapy was not comparable in the two groups. In patients who underwent both pelvic and para-aortic lymphadenectomy, 77% received chemotherapy whereas this was given to only 45% of patients who underwent pelvic lymphadenectomy alone. This study suggests both pelvic and para-aortic lymphadenectomy are beneficial in comparison with patients who undergo pelvic lymphadenectomy alone, but it does not imply that extensive lymphadenectomy improves survival in comparison with no lymphadenectomy. Risk factors are used to determine the indication for adjuvant radiation therapy, as the majority of patients are at low risk of recurrence. Low-risk disease (Stage I, grade 1 or 2 with no or superficial myometrial invasion) does not require adjuvant radiation therapy, as demonstrated in a Danish cohort study of low-risk women, with 96% five-year survival after surgery alone [40]. A seminal Norwegian trial [41], which included 621 women treated after surgery with vaginal brachytherapy, indicated that overall survival was not improved by additional external beam radiation therapy (EBRT), although it did reduce the risk of pelvic recurrence. Three large randomized trials of pelvic radiation therapy versus no further treatment after surgery have determined the role of radiation therapy based on risk factors, and have led to reduced indications for adjuvant radiation therapy: the PORTEC trial [42], the US GOG#99 trial [43], and the UK MRC ASTEC trial [44]. All of these trials reported a significant reduction in the rates of vaginal and pelvic recurrence with EBRT, but without survival benefit. EBRT added to the risk of long-term morbidity. PORTEC and ASTEC trials had similar recurrence and survival rates without lymphadenectomy, compared with GOG#99 that included patients with documented node-negative disease. PORTEC-1 showed that most pelvic relapses were located in the vaginal vault (75%), and that salvage rates were high in women who had not had previous radiation therapy [45]. The PORTEC-2 trial randomized 427 women with high–intermediate risk factors to EBRT or vaginal brachytherapy alone [46]. This trial showed that vaginal brachytherapy had excellent vaginal control rates (< at 5 years for both EBRT and vaginal brachytherapy with adverse and significantly better of of life of patients in the brachytherapy the as those of an population Vaginal brachytherapy has EBRT as standard adjuvant treatment for patients with high–intermediate risk of any EBRT or vaginal brachytherapy for risk disease recurrence rates for intermediate risk disease, of which but without a difference in survival has been by a Danish population study A patient study showed that are to a treatment relapse The seminal trial the use of both EBRT and adjuvant chemotherapy compared with EBRT alone for patients with risk factors (grade 3 or deep invasion or adverse This trial was in a with the Italian trial trials comparing adjuvant EBRT alone with adjuvant chemotherapy alone have not any difference in overall or survival the and trial reported a significant in survival at 5 with the of chemotherapy to EBRT, and a for a in five-year overall survival and trials are currently the of EBRT or chemotherapy alone or combined EBRT and chemotherapy for patients with high-risk or advanced stage disease results of the trial patients with Stage I II endometrial cancer with high intermediate or high-risk factors, comparing vaginal brachytherapy plus of with pelvic showed no in survival or overall survival between the at a of 50% of the trial population had grade disease with a five-year survival of In the trial, patients with high-risk Stage I II or with Stage III endometrial cancer were randomized to pelvic EBRT alone or EBRT with two of followed by of and patients in and results are in In the ongoing patients with node-negative endometrial cancer with high-risk are randomized to adjuvant chemotherapy of or with or without brachytherapy in both These trials will answer of the use and of adjuvant therapy for women with high-risk endometrial cancer. In adjuvant radiation therapy is not indicated for patients with grade tumors and no more than 50% myometrial invasion, or for those with only a risk For patients with high–intermediate risk factors least two of the age deep myometrial invasion, grade 3, serous or clear cell vaginal brachytherapy alone is to EBRT, excellent vaginal control without on of In patients with disease or more risk factors, Stages II and the role of adjuvant with or without radiation therapy, is currently being investigated. This has been in the but a of randomized trials a total of women has no survival benefit for adjuvant therapy in endometrial cancer A randomized trial of women also to any survival benefit Patients with Stage II disease are generally in a similar to patients with Stage I disease. Historically, radical bilateral bilateral pelvic lymphadenectomy, and aortic node dissection can be used as primary treatment for cervical involvement. However, this is by the medical from one of the retrospective studies could not any survival benefit from radical hysterectomy for patients with cervical involvement in comparison with simple or modified radical hysterectomy Since radical hysterectomy the risk of adverse surgical treatment in patients with cervical involvement further MRI scanning is to bladder involvement and local indicate excellent results for this with no benefit from the of radiation for patients with negative nodes is usually reserved for patients with nodes and/or or surgical However, therapy followed by a less extensive simple hysterectomy can an The for adjuvant has not been in a randomized trial, but a study reported improved survival for patients with Stage II endometrial cancer when adjuvant was used after radical and simple hysterectomy If surgery is not considered because of tumor extension, full pelvic and brachytherapy, as in cervical cancer, may be Most patients with Stage III endometrial cancer are by complete surgical resection of all metastatic disease, followed by EBRT and/or chemotherapy. The randomized trial included patients with Stages III and disease and tumor up to 2 and compared abdominal radiation with adjuvant chemotherapy of and showed a survival benefit for chemotherapy estimated five-year although rates were high in both [28]. chemotherapy and is used to reduce the risk of Retrospective studies have pelvic recurrence rates when EBRT was when using chemotherapy and current ongoing trials are the of and of chemotherapy and radiation therapy. A recent randomized trials women with primary FIGO Stage endometrial cancer who received primary surgery showed that chemotherapy survival time after primary surgery by approximately to evaluating women, mainly Stage III compared adjuvant chemotherapy with adjuvant one trial evaluating women mainly Stage III compared two chemotherapy versus in women who had all adjuvant and one trial no and were longer with adjuvant chemotherapy compared with adjuvant In the on survival in of chemotherapy were not different for Stage III and or Stage and This evidence was of from one trial showed that women adjuvant chemotherapy were more to and adverse and and more to treatment, than those adjuvant There was no significant difference in deaths between the chemotherapy and treatment There was no clear difference in survival between groups in the one trial that compared versus A large trial evaluating adjuvant chemotherapy alone of compared with chemotherapy during and after radiation therapy as used in for Stage III endometrial cancer has and results are in Patients with presumed Stage III disease because of adnexal involvement should have full surgical staging and expert examination of the as primary tumors of both the and the may be should be and based on the stage of each tumor. Patients with clinical Stage III endometrial carcinoma that is not to be by of vaginal or parametrial extension are treated primarily by pelvic with or without chemotherapy therapy has been should be considered for those patients whose disease now appears to be Patients with Stage disease based on intraperitoneal spread benefit from surgery only if there is no tumor chemotherapy is an particularly if is and/or morbidity is considered chemotherapy should be based on the trial above [28]. Patients with evidence of metastases are usually with or therapy if grade 1 and/or chemotherapy is the treatment of in disease as well as in disease. The of and and

This study evaluated the immunohistochemical expression of human telomerase reverse transcriptase (hTERT) in endometrial carcinoma and atypical endometrial hyperplasia, and related it to the expression of topoisomerase (TP)IIalpha (a proliferation associated enzyme); apoptosis as determined by the frequency of apoptotic bodies (ABI); mitotic counts; and other clinicopathologic variables. Immunoreactivity for hTERT and TPIIalpha as well as ABI were assessed in 57 endometrial samples (12 atypical hyperplasias, 33 endometrioid carcinomas, 12 serous/clear cell carcinomas). hTERT immunoreactivity, TPIIalpha labeling indices (LI), ABI, and ratios of the indices (ABI/TPIIalpha LI) increased from atypical hyperplasias to endometrioid carcinomas to serous/clear cell carcinomas (p < 0.0001 for each variable). hTERT expression increased with ABI (p < 0.0001), TPIIalpha LI (p = 0.0019), ABI/TPIIalpha ratios (p < 0.0001), and grade (p = 0.0005), but not with FIGO stage (p = 0.2775). TPIIalpha LI, ABI, and ratios were related to high grade (p = 0.0001 for each variable), but not with FIGO stage (p = 0.7362, p = 0.7554, and p = 0.7405, respectively). TPIIalpha LI and ABI were significantly correlated in atypical hyperplasias (p = 0.0004), endometrioid carcinomas (p < 0.0001), and serous/clear cell carcinomas (p = 0.024). Immunostaining levels for hTERT were similar in atypical hyperplasias and grade 1 endometrioid carcinomas (p = 0.1956). These results suggest that hTERT expression is closely related to proliferation, apoptosis, and high grade in endometrial carcinomas, reflecting cell cycle deregulation in endometrial carcinogenesis.

Active surveillance of prostate cancer patients involves subjecting them to multiple prostate biopsies, and we sought to investigate the effects of this on functional outcomes after robotic-assisted radical prostatectomy (RARP). Between May 2009 and December 2009, 367 patients who consecutively underwent RARP by a single surgeon were divided into two groups, one that had single prostate biopsy and another multiple biopsies before RARP. The groups were matched for significant clinicopathologic preoperative variables, and only premorbidly potent low-risk cases that underwent nerve sparing were included. This left 50 and 23 patients for analysis in the single and multiple biopsy groups, respectively. The primary endpoint was potency and continence at 3 and 6 months after surgery. We found continence rates of 84% (83%) and 94% (96%) for single (multiple) biopsy groups at 3 and 6 months, respectively (P=0.88, P=0.77). Multiple biopsy patients had worse postoperative erectile function at 6 months (57% versus 80%, P=0.03). Men subject to multiple preoperative biopsies are more likely to become impotent postoperatively than those who undergo surgery after a single biopsy. This should be borne in mind when counseling men regarding repeat biopsy as part of an active surveillance strategy.

Background: Endometrial cancer is malignant epithelial neoplasm originating from endometrium; endometrial cancer is the sixth most common cancer in women and the fifteenth most common cancer worldwide. The aim of study is to evaluate the expression of P16 IHC in endometrial carcinoma; and its diagnostic role in different histopathological types of endometrial carcinoma. Method: Retrospective study of 70 cases with collection of paraffin embedded tissue blocks and clinical data of patients with endometrial carcinoma and endometrial hyperplasia. H&E staining of slides done to confirm the histopathological diagnosis by specialist pathologist and then stained immunohistochemically for P16 marker. Results: In the current study, the average age of women was 32 to 78 years with a mean age of 53.42. More than half of the women with endometrial carcinoma (EC) (66.6%) presented in the age group between 50 and 70 years, half of the patients with atypical hyperplasia (50%) fall in the same age group as endometrial carcinoma, and the rest of the atypical hyperplasia patients and 65% of those without atypia presented in younger ages (30-50 years’ age group). (63.3%) of patients with endometrial cancer had postmenopausal bleeding; 70% of patients with atypical endometrial hyperplasia and 75% of those without atypia had excessive monthly bleeding (HMB). Histopathology correlated with patient age and clinical presentation. P16 immune marker expression did not correlate with stage at diagnosis of endometrial cancer in TAH & BSO instances. All endometrial serous carcinoma and more than half of EEC had positive p16 IHC. Endometrial hyperplasia had no P16 IHC expression, although more than half of endometrial cancer cases did. Conclusion: All endometrial serous carcinomas expressed high P16 IHC stain. More than half of endometrioid carcinomas had p16 IHC stain, with significant expression in high-grade morphological sections (FIGO 3). Most low-grade endometrioid carcinomas are P16-negative. P16 loss in all endometrial hyperplasia. P16 immunohistochemistry marker aids endometrial carcinoma diagnosis.