Over the last decade, increasing evidence highlights the role of the host immune system in the control of tumor growth and the prognostic implications of tumor infiltrating lymphocytes (TILs) in ...ovarian cancer. Most data support a better prognosis with accumulation of CD3+ and CD8 + TILs and a poor outcome associated with increased regulatory T cells. However, only a small number of studies have focused on the effect of neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment. This review will provide an update on the prognostic value of TIL subpopulations at diagnosis and a comprehensive overview of the recent studies evaluating the impact of neoadjuvant chemotherapy on TILs and their relationship to clinical outcome in advanced ovarian cancer. This information could help in future investigations of immunotherapy as maintenance following primary treatment.
Risk-assessment of endometrial cancer (EC) is based on clinicopathological factors and molecular subgroup. It is unclear whether adding hormone receptor expression, L1CAM expression or CTNNB1 status ...yields prognostic refinement.
Paraffin-embedded tumour samples of women with high-risk EC (HR-EC) from the PORTEC-3 trial (n = 424), and a Dutch prospective clinical cohort called MST (n = 256), were used. All cases were molecularly classified. Expression of L1CAM, ER and PR were analysed by whole-slide immunohistochemistry and CTNNB1 mutations were assessed with a next-generation sequencing. Kaplan-Meier method, log-rank tests and Cox's proportional hazard models were used for survival analysis.
In total, 648 HR-EC were included. No independent prognostic value of ER, PR, L1CAM, and CTNNB1 was found, while age, stage, and adjuvant chemotherapy had an independent impact on risk of recurrence. Subgroup-analysis showed that only in NSMP HR-EC, ER-positivity was independently associated with a reduced risk of recurrence (HR 0.33, 95%CI 0.15-0.75).
We confirmed the prognostic impact of the molecular classification, age, stage, and adjuvant CTRT in a large cohort of high-risk EC. ER-positivity is a strong favourable prognostic factor in NSMP HR-EC and identifies a homogeneous subgroup of NSMP tumours. Assessment of ER status in high-risk NSMP EC is feasible in clinical practice and could improve risk stratification and treatment.
Mueller polarimetric imaging enables the detection and quantification of modifications of the collagen fibers in the uterine cervix due to the development of a precancerous lesion. This information ...is not accessible through the use of the classic colposcope, a low magnification microscope used in current practice for cervical cancer screening. However, the in vivo application of Mueller polarimetric imaging poses an instrumental challenge: the device should be sufficiently compact, while still being able to perform fast and accurate acquisition of Mueller matrices in real-world conditions. In this study, the first wide field Mueller Polarimetric Colposcope (MPC) for the in vivo analysis of uterine cervix is presented. The MPC has been fabricated by grafting a miniaturized Mueller polarimetric imager on a classic colposcope. This new imaging tool performs the fast acquisition of Mueller polarimetric images, thus eliminating any blurring effects due to patient movements. It can be easily used by a practitioner with little change to their existing practice. Finally, the MPC was tested in vivo on a number of patients in the field.
Pathobiology of ovarian carcinomas Devouassoux‐Shisheboran, Mojgan; Genestie, Catherine
Ai zheng,
01/2015, Letnik:
34, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, ...and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers (carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular basis of ovarian carcinomas represents the first step in the development of targeted therapies in the near future.
Objective
The aim of this study was to assess the outcomes of a large series of patients treated conservatively for stage II or III serous borderline tumors of the ovary (SBOTs) with a long-term ...follow-up.
Methods
Patients with SBOTs and peritoneal implants, treated in or referred to our institution, were retrospectively reviewed. Outcomes of patients treated conservatively (preservation of the uterus and at least a part of one ovary) to promote subsequent fertility were specifically analyzed.
Results
Between 1971 and 2017, 212 patients were identified and followed-up. Among these patients, 65 underwent conservative treatment; eight patients had invasive implants. Among patients treated conservatively, 38 (58%) patients recurred. Twenty-eight recurrences were observed under the form of borderline tumor on the spared ovary and/or noninvasive implants, but eight patients had a recurrence under the form of invasive disease. Compared with radical surgery, the use of conservative treatment (
p
< 0.0001) was a prognostic factor on disease-free survival (DFS), but without an impact on overall survival (OS). Nevertheless, three deaths occurred. Twenty-four pregnancies (13 spontaneous) were observed in 20 patients (29 patients wanted to become pregnant).
Conclusion
In this series collecting the largest number of patients undergoing conservative surgery for stage II/III SBOTs, spontaneous pregnancies can be achieved after conservative treatment of advanced-stage disease, but the recurrence rate is high and three deaths were observed. These patients were spared their fertility but with a high rate of recurrence. Uncertainties regarding the safety of conservative treatment should be exposed to these patients.
Background
Most frequent borderline ovarian tumors are serous and mucinous subtypes. Less frequent borderline diseases are endometrioid, clear-cell, and Brenner tumors (BBOT). Very little is known ...about the latter subtype, and most studies include very short series or case reports. The aim of this study is to determine the prognosis of a continuous series of BBOT and analyze data published in the literature on this rare entity.
Patients and Methods
A retrospective review of patients with BBOT treated or referred to our institutions was conducted. A centralized histological review by a reference pathologist and data on the clinical characteristics, management, and outcomes of patients were required for inclusion.
Results
Overall, 17 patients were identified. Median age was 62 (range 42–85) years. Six patients underwent unilateral salpingo-oophorectomy, and 11 bilateral salpingo-oophorectomy +/− hysterectomy and/or staging surgery. In total, 16 patients had unilateral tumor, and all patients had stage I disease. Stromal microinvasion was observed in three cases. Median follow-up was 60 months (range 7–118 months). One patient developed a recurrence in contralateral ovary after unilateral salpingo-oophorectomy. One patient had previous history of urothelial tumor.
Conclusions
Peritoneal staging surgery is not required because all patients reported had stage I disease. One recurrence occurred. When reviewing all the 82 cases reported in the literature (including ours), 9% had previous history or synchronous urothelial tumor, suggesting the need to carefully check for urological disease in patients with BBOT.
Female adnexal tumor of probable Wolffian origin is a rare tumor listed in the 2016 WHO classification of the female reproductive tract. It does not have a WHO-recognized counterpart in the male ...urogenital tract. However, some cases of male adnexal tumors have been described in the literature. We present the case of a 41-year-old male who presented with a 2-cm nodule in the testicle. LDH, HCG, and AFP blood levels were normal. Gross examination showed an intratesticular, whitish, microcystic, firm, and encapsulated nodule of 2 cm. Microscopically, the tumor was well circumscribed, solid, and microcystic. In the solid areas, cells were fusiform or polygonal with an eosinophilic pale cytoplasm and a regular oval nucleus. Cysts were surrounded by a fibromuscular stroma and lined by a single layer of cylindrical epithelium, with apical cilia. On immunohistochemistry, tumor cells expressed AE1/AE3 and vimentin and were negative for calretinin, epithelial membrane antigen (EMA), and inhibin. All the differential diagnoses at this localization being ruled out, the tumor was compared to a female adnexal tumor of probable Wolffian origin. Both tumors had approximately the same morphological and immunohistochemical profile. Naming our tumor MATPWO is therefore justified, but it remains of a probable origin because further studies need to be performed in order to certify this hypothesis.
Background
At diagnosis, tumor-infiltrating lymphocytes (TILs) are prognostic in epithelial ovarian cancer (EOC). We recently demonstrated that neoadjuvant chemotherapy (NACT) significantly increased ...stromal TILs. Here, we investigated the impact of NACT on immune subpopulations with a particular focus on the balance of immune-reactive to tolerant subpopulations.
Materials and methods
Tissue microarrays of EOC (145 pre-NACT, 139 post-NACT) were analyzed for CD3+, CD8+, FOXP3+, CD68+, and CD163+ by immunohistochemistry and CD4+ cells from deduction. Stromal TILs scored as percentage of stromal area, while intra-epithelial TILs scored as number of TILs in contact with tumor cells/HPF. Differences were evaluated by Wilcoxon or Chi square tests, Wilcoxon signed-rank for paired analyses, and cox model for PFS and OS.
Results
NACT significantly increased stromal CD3+ (
p
= 0.003) and CD8+ (
p
= 0.001) and intra-epithelial CD8+ (
p
= 0.022) and CD68+ (
p
= 0.0003) infiltration in unmatched samples and among paired samples for stromal CD3+ and CD8+. Neither CD3+, CD8+, CD4+, and CD68+ nor CD163+ expression correlated with outcome at diagnosis or post NACT. Using median value as a cut-off, high stromal CD8+/FOXP3+ ratio (HR = 0.59;
p
= 0.017) and high stromal CD3+/FOXP3+ ratio post NACT were associated with prolonged PFS (
p
= 0.0226). The more the balance shifted in favor of effector versus regulatory TILs, the better the survival. Similarly, high CD68+/CD163+ ratio post NACT improved PFS (
p
= 0.0445).
Conclusion
NACT has a significant impact on the balance of immune-reactive to immune-tolerant subpopulations and a high ratio of CD8+/FOXP3+, CD3+/FOXP3+, and CD68+/CD163+ post NACT was significantly associated with improved outcomes. Whether this could select patients for immunotherapy in the post-operative setting should be investigated.
Background
Clear cell borderline ovarian tumor (CCBOT) is one of the rarest subtypes of borderline ovarian malignancies. The aim of this study was to determine the prognosis of a series of CCBOT.
...Patients and Methods
A retrospective review of patients with CCBOT treated or referred to our institutions. A centralized histological review by a reference pathologist and data on the clinical characteristics, management, and outcomes of patients were required for inclusion.
Results
Nineteen patients were identified. Median age was 62 (range 36–83) years. Four patients underwent a conservative surgery and 14 a bilateral salpingo-oophorectomy +/– hysterectomy (unknown in 1 case). One patient had bilateral tumor, and all cases were stage-I disease. All CCBOTs showed an adenofibromatous pattern. Stromal microinvasion was observed in seven cases and intraepithelial carcinoma in two cases. Endometriosis was histologically associated in one case. The median follow-up was 76 (range 6–231) months. No recurrence occurred. Two patients died of intercurrent disease.
Conclusions
Peritoneal staging procedures should always be associated, but restaging surgery could be omitted if there was no suspicious lesion in the peritoneum during initial surgery, since all patients reported had stage-I disease. Fertility-sparing surgery appears to be a safe alternative in young patients. Synchronous endometrial disorders with atypia are infrequent. Prognosis is generally excellent, and long-term risk of recurrence is low. The two recurrences described in literature occurred in stage-IC diseases, highlighting the importance of avoiding perioperative rupture.