Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

Pathological reporting of cystectomy lymph nodes: a retrospective analysis of experience in Paris.

PURPOSE: Pathological evaluation of pelvic lymph node (LN) dissection (PLND) is important for management of cystectomy patients. However, challenges such as unclear interobserver variability of LN counting remain. Here, we assess interobserver variability of LN measures and their clinical utility, with a focus on variant histology. METHODS: We retrieved radical cystectomy cases with PLND between 2010 and 2016 and reevaluated pathological parameters; number of total and metastatic LN, LN density (LND), length of metastatic LN and metastases, extranodal extension (ENE). RESULTS: We report 96 patients: median age of 71a, 34 cases pN+, 36 cases with any extent of variant histology, median follow-up 10 months. Perivesical LN were only rarely identified, but frequently metastatic (4/9). Variant histology (34 cases) frequently exhibited LN metastasis (53% of pN+ cases). Interobserver variance was poor for total LN (kappa = 0.167), excellent for positive LN (0.85) and pN staging (0.96), and mediocre for LND (0.53). ROC analysis suggests that both LND and the sum of LN metastasis length may predict outcome (AUC 0.83 and 0.75, respectively). CONCLUSION: Our study confirms the notion of LND as a prognostic measure, but cautions due to strong interobserver variance of LN counts. The sum length of LN metastases could be a measure that is independent of LN counts. We find that microscopically identified perivesical LN merit particular attention. In summary, our study highlights current challenges in pathological reporting of PLND, confirms previous observations and forms a basis for further studies.

Standardizing immunohistochemistry methodology for evaluation of PD-1 and PDL-1 expression in upper tract urothelial carcinoma.

INTRODUCTION: Controversy regarding the prognostic and/or predictive role of PD-1 and PD-L1 expression for upper tract urothelial carcinoma (UTUC) could partly be explained by inconsistencies in the immunohistochemistry (IHC) methodology. Objective is to standardize the methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC patients. MATERIALS AND METHODS: Twenty-two cases treated with radical nephroureterectomy between 1996 and 2015 at 11 French hospitals were randomly selected to compare different methodologies for evaluation of PD-1 and PD-L1 expression. IHC was carried out on whole tissue sections and 0.6 mm- or 2 mm-core tissue micro-arrays (TMAs) using PD-1 NAT105 and PD-L1 28.8 or E1L3N on both tumor cells and tumor-infiltrating immune cells (TILs). Results obtained with whole tissue sections (WTS) were compared to those obtained with 0.6 mm- and 2 mm-core TMAs. Concordance was evaluated using Kappa coefficient. RESULTS: For evaluation of PD-1 and PD-L1 expression, the best concordance with WTS was observed using the PD-1 NAT105 and PD-L1 28.8 antibody on 2 mm-core TMAs, with 5% cut off for positivity on TILs and tumor cells, respectively (Kappa = 0.8). CONCLUSIONS: The most accurate methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC may be based on 2 mm-core TMAs using NAT105 and 28.8 antibodies with a 5% cut off for positivity on TILs and tumor cells, respectively.

Absence of predictable long-term molecular effect of ulipristal acetate (UPA) on the endometrium.

RESEARCH QUESTION: What are the effects of ulipristal acetate (UPA) on the expression of endometrial proliferation and maturation markers? DESIGN: A total of 45 endometrium-containing blocks of hysterectomy samples from non-menopausal women with a diagnosis of moderate to severe symptoms of uterine fibroids: 14 women operated on at the end of a 3-month course of UPA; four women who had discontinued UPA treatment 1-12 months before surgery; 27 control unexposed samples (14 in the proliferative and 13 in the secretory phase). Immunohistochemical staining of Ki67, vascular endothelial growth factor-receptor 2 (VEGFR2), oestradiol receptor, progesterone receptor, interleukin-15 (IL-15), indoleamin-2,3-dioxygenase (IDO) and C-C motif chemokine ligand-2 (CCL2) markers were analysed in both endometrial compartments and layers. RESULTS: Under UPA, oestradiol receptor and progesterone receptor expression is similar to the proliferative phase in both layers, although with a decrease in cell proliferation. IL-15, IDO and CCL2 expressions are similar to the proliferative phase, suggesting a progesterone-antagonist effect of UPA. VEGFR2 staining suggests a trend to a mixed agonist-antagonist effect. No significant difference is observed in the post-UPA proliferative phase group compared with the control group in both layers of the endometrium. CONCLUSION: The effect of 3-month UPA treatment is mostly progesterone receptor antagonist-like. After treatment is discontinued, there are no signs of any long-term effects of this molecule on endometrial proliferation and maturation. Therefore, UPA may be administered to women willing to conceive in the short term without consequences for further implantation.

[Comparison of UICC and AJCC 8th edition TNM classifications in uropathology]. / Comparaison des classifications TNM des 8es éditions de l'UICC et de l'AJCC en uropathologie.

The pTNM stage is one of the most important parameters in the handling of tumor patients. The pathologist plays a major role in the determination of the stage. The classifications undergo an evolution according to the state of art. The TNM system is used worldwide and allows to precise the tumor (T) and lymph node stage and the presence of distant metastasis. This system helps to stratify patient groups and determine their prognosis. In 2017, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) published their 8th edition. Unluckily several differences exist between both classifications. The UICC neglected to make several recommendations according to the International Society of Urological Pathology (ISUP) decisions, which organises the consensus in uropathology.

Comparison of cell cycle progression score with two immunohistochemical markers (PTEN and Ki-67) for predicting outcome in prostate cancer after radical prostatectomy.

PURPOSE: Previous studies of the cell cycle progression (CCP) score in surgical specimens of prostate cancer (PCa) in patients treated by radical prostatectomy (RP) demonstrated significant association with time to biochemical recurrence (BCR). In this study, we compared the ability of the CCP score and the expression of PTEN or Ki-67 to predict BCR in a cohort of patients treated by RP. Finally, we constructed the best predictive model for BCR, incorporating biomarkers and relevant clinical variables. MATERIALS AND METHODS: The study population consisted of 652 PCa patients enrolled in a retrospective cohort and who had RP surgery in French urological centers from 2000 to 2007. RESULTS: Among the 652 patients with CCP scores and complete clinical data, BCR events occurred in 41%, and the median time from surgery to the last follow-up among BCR-free patients was 72 months. In univariate Cox analysis, the continuous CCP score and positive Ki-67 predicted recurrence with a HR of 1.44 (95% CI 1.17-1.75; p = 5.3 × 10-4) and 1.89 (95% CI 1.38-2.57; p = 1.6 × 10-4), respectively. In contrast, PTEN expression was not associated with BCR risk. Of the three biomarkers, only the CCP score remained significantly associated in a multivariable Cox model (p = 0.026). The best model incorporated CAPRA-S and CCP scores as predictors, with HRs of 1.32 and 1.24, respectively. CONCLUSION: The CCP score was superior to the two IHC markers (PTEN and Ki-67) for predicting outcome in PCa after RP.

Large nested variant of urothelial carcinoma: a clinicopathological study of 36 cases.

AIMS: The large nested variant of urothelial carcinoma (LNUC) has been added to the World Health Organization (WHO) 2016 classification. Scant data exist, and little is known about its clinical behaviour. MATERIAL AND RESULTS: Cases fulfilling the morphological criteria of LNUC were collected. Pure and mixed cases (i.e. with other patterns of invasive UC) were studied. Immunohistochemical staining with cytokeratin (CK)7, p63, GATA-3, CK20, p53 and Ki-67 was performed. Included were 26 cystectomies (RC) and 10 resections (TURB) belonging to 36 patients with an average age of 66.7 years. Fourteen (39%) were pure LNUCs, and 22 (61%) displayed mixed features. Seventy per cent of the TURBs had pT2 tumours, while 58% of RCs had extravesical disease (≥pT3 and/or ≥pN1), with the rate of advanced disease being higher in mixed (69%) in comparison to pure cases (40%). Similarly, 38% of mixed cases had nodal metastases in comparison to 20% of pure cases. Overall, eight patients (24%) died of disease at a mean interval time of 21.7 months and seven patients (21%) showed recurrence or metastases. Disease progression was significantly higher in mixed cases (55 and 31% in mixed and pure cases, respectively). Positive staining was: CK7 = 87.5%, CK20 = 72%, GATA-3 = 91%, P63 = 100%, p53 = 56% and Ki-67 = mean of 16%. CONCLUSION: Despite the bland cytological appearance and deceptive pattern of invasion of the LNUC, our study validates its fully malignant potential with metastatic spread and tumour-related deaths. Distinguishing mixed from pure LNUCs seems to be of value. LNUCs show comparable immunophenotype to both conventional urothelial carcinoma and the nested variant of urothelial carcinoma.

Immunochemical and molecular assessment of urothelial neoplasms and aspects of the 2016 World Health Organization classification.

The new World Health Organization classification of tumours of the urinary system and male genital organs (4th edn) has several changes from previous versions, and was published in January 2016. New pathways have been discovered in the development of bladder cancer, and were included in this new classification. Guidance from the International Collaboration on Cancer Reporting (ICCR) helped to clarify open questions, in conjunction with the new classification. The histological groups of urothelial carcinoma evolved. Grading remained the same, despite controversy among European urologists. Substaging of pT1 tumours is recommended for the first time, and the ICCR has made recommendations on how to report this. Furthermore, worldwide advice has been published on the use of immunohistochemistry, and recommendations have been made to try to standardize the handling of bladder cancer from a histopathological point of view. At a molecular level, bladder cancer groups have been stratified, and an upcoming molecular classification permits a novel view of this malignancy. This review will try to summarize the most important changes.

Apparent diffusion coefficient value is a strong predictor of unsuspected aggressiveness of prostate cancer before radical prostatectomy.

PURPOSE: To evaluate the use of multiparametric MRI (mp MRI) parameters in order to predict prostate cancer aggressiveness as defined by pathological Gleason score or molecular markers in a cohort of patients defined with a Gleason score of 6 at biopsy. METHODS: Sixty-seven men treated by radical prostatectomy (RP) for a low grade (Gleason 6) on biopsy and mp MRI before biopsy were selected. The cycle cell proliferation (CCP) score assessed by the Prolaris test and Ki-67/PTEN expression assessed by immunohistochemistry were quantified on the RP specimens. RESULTS: 49.25 % of the cancers were undergraded on biopsy compared to the RP specimens. Apparent diffusion coefficient (ADC) < 0.80 × 10(-3) mm(2)/s (P value 0.003), Likert score >4 (P value 0.003) and PSA density >0.15 ng/ml/cc (P value 0.035) were significantly associated with a higher RP Gleason score. Regarding molecular markers of aggressiveness, ADC < 0.80 × 10(-3) mm(2)/s and Likert score >4 were also significantly associated with a positive staining for Ki-67 (P value 0.039 and 0.01, respectively). No association was found between any analyzed MRI or clinical parameter and the CCP score. CONCLUSION: Decreasing ADC value is a stronger indicator of aggressive prostate cancer as defined by molecular markers or postsurgical histology than biopsy characteristics.

[From new genetic and histological classifications to direct treatment]. / Carcinome urothélial : des classifications histologiques et moléculaires vers un traitement adéquat.

The most important criterion for optimal cancer treatment is a correct classification of the tumour. During the last three years, several very important progresses have been made with a better definition of urothelial carcinoma (UC), especially from a molecular point of view. We start having a global understanding of UC, although many details are still not completely understood.

Multiparametric Magnetic Resonance Imaging Predicts Postoperative Pathology but Misses Aggressive Prostate Cancers as Assessed by Cell Cycle Progression Score.

PURPOSE: We identified prognostic biomarkers in prostate cancer by a radiogenomics strategy that integrates gene expression using the cell cycle progression score and medical images. MATERIALS AND METHODS: We obtained institutional review board approval and written informed consent from 106 men with prostate cancer, including 60% at low risk, who underwent multiparametric magnetic resonance imaging before radical prostatectomy was done and a cell cycle progression score was determined. The correlation between the results of multiparametric magnetic resonance imaging and Gleason grade or cell cycle progression score was assessed by logistic regression. RESULTS: Patients with primary Gleason grade greater than 3 had a longer median maximal tumor diameter (13 vs 10 mm) and a lower median apparent diffusion coefficient (0.745 vs 0.88×10(-3) mm2 per second, each p=0.0001) than those with primary Gleason grade 3 or less. Maximal diameter 10 mm or greater (OR 4.9, 95% CI 1.7 to 14.0, p=0.0012) and apparent diffusion coefficient 0.80×10(-3) mm2 per second or less (OR 7.5, 95% CI 3.0 to 18.7, p<0.0001) were significantly associated with primary Gleason grade greater than 3. The combined measure of maximal diameter less than 10 mm and apparent diffusion coefficient greater than 0.80×10(-3) mm2 per second identified only index lesions harboring primary Gleason grade 3. However, 7 of those lesions showed a molecular pattern of high risk lethal prostate cancer (cell cycle progression score greater than 0). CONCLUSIONS: Multiparametric magnetic resonance imaging is able to predict low and high risk Gleason scores in the tumor. However, the cell cycle progression score did not completely match the imaging result. These findings suggest that management of early stages prostate cancer could strongly benefit by performing magnetic resonance imaging targeted biopsy coupled with molecular analysis.

Cyclin A1 expression predicts progression in pT1 urothelial carcinoma of bladder: a tissue microarray study of 149 patients treated by transurethral resection.

AIMS: To evaluate the immunoexpression of cyclin A1 in pT1 urothelial carcinomas of the bladder (UC) from a cohort of patients treated by transurethral resection of the bladder (TURB), to determine its value in predicting tumour recurrence, tumour progression, or systemic metastases. METHODS AND RESULTS: Five tissue microarrays (TMAS) were constructed from representative paraffin blocks of high-grade pT1 UC from 149 consecutive patients. Cyclin A1 immunoexpression was evaluated as the percentage of tumour cells with positive nuclear staining estimated at each TMA spot. The cutoff for cyclin A1 positivity was set at 10% of cells. Outcome variables included tumour recurrence and tumour progression as the primary endpoints. Cyclin A1 positivity was associated with tumour progression but not with tumour recurrence or the presence of adjacent carcinoma in situ in the biopsy. Also, patients with pT1b at biopsy and cyclin A1 expression showed higher progression rates than patients with pT1a at biopsy and without cyclin A1 expression, respectively. Combining pT1 stage at biopsy and cyclin A1 expression more accurately predicted tumour progression than pT1 stage at biopsy alone and cyclin A1 expression alone. CONCLUSIONS: Cyclin A1 immunoexpression is of potential utility in predicting disease progression in patients with pT1 UC.

The surgical approach can be determined from the pathological specimen obtained after open or robot-assisted laparoscopic radical prostatectomy.

PURPOSE: To assess the surgical approach using the pathological specimen obtained after open radical prostatectomy (ORP) or robot-assisted radical prostatectomy (RALRP). METHODS: A prospective study has been performed in patients who underwent either ORP or RALRP for localized prostate cancer. Two dedicated uro-pathologists, blinded to the surgeons and the operating rooms' schedules, analyzed the pathological specimens according to the Stanford protocol. Both pathologists also determined the surgical approach used based on several criteria pertaining to the pathological specimen. RESULTS: Overall, 117 patients with a median age of 63 years were included. The main characteristics (i.e., Gleason score, pTNM stage, preoperative PSA and margin) were comparable in both groups (p > 0.05). Pathologists 1 and 2 were able to significantly assess the surgical procedure from the pathological specimen provided (in 76.1 and 69.2 % of cases, respectively). Pathologist 1 had a better performance than pathologist 2 (AUC 0.75, IC 95 % [0.67-0.83] vs. AUC = 0.68 IC 95 % [0.59-0.77]) (p = 0.017). The κ index of the inter-observer agreement was satisfactory (0.76). In a univariate analysis, the criteria linked to the pathologist's assessment were as follows: macroscopic integrity of the specimen (p = 0.04), presence of periprostatic fat (p = 0.04), width of periprostatic tissue (p < 0.001) and nerve-sparing status (p < 0.001). CONCLUSION: It was possible to determine the surgical procedure from the analysis of the specimen obtained after a radical prostatectomy. In view of these data and from this perspective, one could infer that there are indeed oncological differences between the robotic and open approaches to radical prostatectomy.

[Benign mimickers of the prostate cancer. Diagnostic challenges]. / Lésions bénignes mimant le cancer de la prostate. Challenges diagnostiques.

The diagnosis of prostate cancer (PCa), especially limited adenocarcinoma on needle biopsy, is often challenging. Before making diagnosis of PCa, it is prudent for the pathologist to consider different benign patterns that may lead to a false positive interpretation. Histoanatomic structures such as seminal vesicles, Cowper's glands and paraganglia along with hyperplasia, atrophy with its different patterns and adenosis may generate difficulties in differential diagnosis. Furthermore, inflammatory processes and post-treatment changes may cause problems. The above entities can in some instances simulate low-grade and less commonly high grade PCa. Knowledge of these patterns and application of appropriate immunohistochemistry will lead the pathologist to a correct diagnosis.

The presence of detrusor muscle in the pathological specimen after transurethral resection of primary pT1 bladder tumors and its relationship to operator experience.

INTRODUCTION: To assess the quality of transurethral resection of bladder tumors (TURBTs) performed by "senior" and "junior" urologists for pT1 tumors in terms of detrusor muscle (DM) presence and recurrence rate at 3 month first cystoscopy (RR-FC). Non-muscle invasive bladder cancer (NMIBC) is a heterogeneous group with differing biological potentials. Tumors invading lamina propria (pT1) have an increased propensity for recurrence and progression. Accurate staging at the time of primary TURBT, including the presence of DM, is crucial to avoid understaging and unnecessary delay in definitive treatment. MATERIALS AND METHODS: We analyzed our maintained bladder tumor database (TURBTs from 2002 to 2009) and selected patients diagnosed with pT1 bladder tumors. Data on surgeon status, tumor characteristics (size, TNM stage 2009, grade, DM presence) and RR-FC were retrieved. Surgeons were stratified into "senior" and "junior" according to the years of prior training. RESULTS: Of the 340 TURBTs for pT1 tumors, "senior" and "junior" surgeons performed 237 (69.7%) and 103 (30.3%), respectively. Overall, 238 (70%) TURBTs had DM in the specimen, including 175 (73.8%) and 63 (61.3%) for the "senior" and "junior" operators, respectively (p = 0.02). The overall RR-FC was 37.4% (n = 127) and was significantly different for DM presence and DM absence (30.7% versus 52.9%; p = 0.01). On multivariate analysis, tumor recurrence was associated with "junior" operator experience independent of the presence or absence of DM (OR = 2.33 [1.45-3.74]) p = 0.01). CONCLUSIONS: The presence of DM in a primary TURBT for pT1 NMIBC is directly associated with operator experience, with an associated increased 3 month recurrence rate for "junior" resectionists.

[Epidemiology, classification and risk factors of endometrial cancer]. / Instabilité des microsatellites dans les cancers de l'endomètre.

MICROSATELLITE INSTABILITY IN ENDOMETRIAL CANCERS The microsatellite instability reflects genetic instability that can be sought in tumors, using two methods, immunohistochemistry and molecular biology. Currently in France, a systematic evaluation of microsatellites is recommended in any endometrial cancer from diagnosis. The interest of this evaluation is threefold: diagnostic, prognostic and therapeutic. The presence of microsatellite instability in endometrial cancer allows to detect Lynch syndrome, a hereditary cancer predisposition syndrome, in some patients. The microsatellite status is essential for establishing the molecular classification of endometrial cancers, a classification which has a well-established prognostic value, and finally it determines the eligibility for immunotherapy.

INSTABILITÉ DES MICROSATELLITES DANS LES CANCERS DE L'ENDOMÈTRE L'instabilité des microsatellites est le reflet d'une instabilité génétique que l'on peut rechercher dans les tumeurs, grâce à deux techniques : l'immunohistochimie et la biologie moléculaire. Actuellement, en France, une évaluation systématique des microsatellites est recommandée dans tout cancer de l'endomètre dès le diagnostic. L'intérêt de cette évaluation est triple : diagnostique, pronostique et thérapeutique. La présence d'une instabilité des microsatellites dans un cancer de l'endomètre permet de détecter chez quelques patientes un syndrome de Lynch, syndrome héréditaire de prédisposition au cancer. Le statut microsatellitaire est indispensable à l'établissement de la classification moléculaire des cancers de l'endomètre, classification qui a une valeur pronostique bien établie, et qui permet de déterminer l'éligibilité à une immunothérapie.

The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review.

The objective of this systematic review was to summarize our current knowledge of the role of immunohistochemistry (IHC) markers for identifying mismatch repair-deficient (MMRd) tumors in endometrial cancer (EC). Identification of MMRd tumors, which occur in 13% to 30% of all ECs, has become critical for patients with colorectal and endometrial cancer for therapeutic management, clinical decision making, and prognosis. This review was conducted by two authors applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the following terms: "immunohistochemistry and microsatellite instability endometrial cancer" or "immunohistochemistry and mismatch repair endometrial cancer" or "immunohistochemistry and mismatch repair deficient endometrial cancer". Among 596 retrieved studies, 161 fulfilled the inclusion criteria. Articles were classified and presented according to their interest for the diagnosis, prognosis, and theragnostics for patients with MMRd EC. We identified 10, 18, and 96 articles using IHC expression of two, three, or four proteins of the MMR system (MLH1, MSH2, MHS6, and PMS2), respectively. MLH1 promoter methylation was analyzed in 57 articles. Thirty-four articles classified MMRd tumors with IHC markers according to their prognosis in terms of recurrence-free survival (RFS), overall survival (OS), stage, grade, and lymph node invasion. Theragnostics were studied in eight articles underlying the important concentration of PD-L1 in MMRd EC. Even though the role of IHC has been challenged, it represents the most common, robust, and cheapest method for diagnosing MMRd tumors in EC and is a valuable tool for exploring novel biotherapies and treatment modalities.

PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases.

Therapeutic strategies for epithelial ovarian cancers are evolving with the advent of immunotherapy, such as PD-L1 inhibitors, with encouraging results. However, little data are available on PDL-1 expression in ovarian cancers. Thus, we set out to determine the PD-L1 expression according to histological subtype. We evaluated the expression of two PD-L1 clones - QR1 and E1L3N - with two scores, one based on the percentage of labeled tumor cells (tumor proportion score, TPS) and the other on labeled immune cells (combined proportion score, CPS) in a consecutive retrospective series of 232 ovarian cancers. PD-L1 expression was more frequent in high grade serous carcinoma (27.5% with E1L3N clone and 41.5% with QR1 clone), grade 3 endometrioid carcinoma (25% with E1L3N clone and 50% with QR1 clone), and clear-cell carcinomas (27.3% with E1L3N clone and 29.6% with QR1 clone) than other histological subtypes with CPS score. Using the CPS score, 17% of cases were labeled with E1L3N vs 28% with QR1. Using the TPS score, 14% of cases were positive to E1L3N vs 17% for QR1. For TPS and CPS, respectively, 77% and 78% of the QR1 cases were concordant with E1L3N for the thresholds of 1%. Overall and progression-free survival between PD-L1 positive and PD-L1 negative patients were not different across all histological types, and each subtype in particular for serous carcinomas expressing PD-L1. Expression of PD-L1 is relatively uncommon in epithelium ovarian tumors. When positive, usually <10% of tumor cells are labeled. QR1 clone and CPS appear the best tools to evaluate PD-L1 expression.

Ulipristal Acetate Modifies miRNA Expression in Both Superficial and Basal Layers of the Human Endometrium.

(1) Background: Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) widely used for emergency contraception and mid- to long-term leiomyoma treatment. The aim of this study was to identify modifications of miRNA expression in superficial and basal layers of the human endometrium at the end of the UPA treatment for at least 3 months. (2) Methods: Microarray miRNA analysis of formalin-fixed, paraffin-embedded hysterectomy tissue samples was conducted, followed by an Ingenuity Pathway Analysis. Samples were divided into three groups: women having had 3 months of UPA treatment (n = 7); and two control groups of UPA-naïve women in the proliferative (n = 8) or secretory (n = 6) phase. (3) Results: The UPA modified the expression of 59 miRNAs involved in the processes of cell cycle, carcinogenesis, and inflammation. Their expression profiles were different in the basal and superficial layers. Most of the processes influenced by the UPA in the basal layer were connected to the cell cycle and immune regulation. (4) Conclusion: Specific changes were observed in both layers of the endometrium in the UPA group. However, the miRNA expression in the basal layer was not consistent with that in the superficial layer. Other large studies analysing the long-term impact of SPRM on endometrial miRNA expression are necessary.