Cases Of Uterine Papillary Serous Carcinoma Research Articles

Minimally Invasive Technique Not Associated with Worse Prognosis in Patients with Stage I Uterine Papillary Serous Carcinoma (UPSC)

Study Objective To determine the role of surgical technique in increasing risk of recurrence in patients with stage I UPSC. Design Using a prospective database and billing records, all cases of UPSC were identified from 2006 through 2021. Standard statistical analysis related the impact of surgical technique and BTL on recurrence risk and progression free survival (PFS) in patients with stage I UPSC. Setting N/A. Patients or Participants All patients with UPSC diagnosed at our center 2006-2021. Interventions N/A. Measurements and Main Results A total of 225 total cases of UPSC were identified, including 118 pts with stage I disease. Six patients (5%) had endometrial intraepithelial carcinoma (EIC), 98 (83%) were stage IA, and 14 (12%) were stage IB. A history of BTL was obtained in 25 pts (21%). Minimally invasive hysterectomy was performed in 99 (84%; 31% robot, 53% laparoscopy). Adjuvant chemotherapy was given to 83 patients (72%) with 31 (256%) receiving 3 cycles or less and 54 (46%) receiving 4-7 cycles. Additionally, 22 (19%) received vaginal brachytherapy and 9 (8%) received whole pelvic radiation. Seventeen patients (14%) experienced recurrence after treatment and 8 (7%) died of disease. No differences in PFS or outcomes were noted between open and minimally invasive methods (P=0.76). Patients who underwent BTL prior to diagnosis were found to have a recurrence rate of 28% vs. 11% in patients without history of BTL (P = 0.03). A multivariate model incorporating known risk factors for recurrence, including use of radiation, chemotherapy, depth of invasion, and LVSI, confirmed that BTL remained a significant predictor of recurrence (OR 3.18; 95% CI 1.02-9.96, P = 0.046). Conclusion No differences in progression free survival were noted between patients who underwent minimally invasive vs. open surgeries in patients with stage I UPSC. However, BTL does not appear to be protective against extra-uterine spread and may change the presenting stage of biologically more aggressive tumors. To determine the role of surgical technique in increasing risk of recurrence in patients with stage I UPSC. Using a prospective database and billing records, all cases of UPSC were identified from 2006 through 2021. Standard statistical analysis related the impact of surgical technique and BTL on recurrence risk and progression free survival (PFS) in patients with stage I UPSC. N/A. All patients with UPSC diagnosed at our center 2006-2021. N/A. A total of 225 total cases of UPSC were identified, including 118 pts with stage I disease. Six patients (5%) had endometrial intraepithelial carcinoma (EIC), 98 (83%) were stage IA, and 14 (12%) were stage IB. A history of BTL was obtained in 25 pts (21%). Minimally invasive hysterectomy was performed in 99 (84%; 31% robot, 53% laparoscopy). Adjuvant chemotherapy was given to 83 patients (72%) with 31 (256%) receiving 3 cycles or less and 54 (46%) receiving 4-7 cycles. Additionally, 22 (19%) received vaginal brachytherapy and 9 (8%) received whole pelvic radiation. Seventeen patients (14%) experienced recurrence after treatment and 8 (7%) died of disease. No differences in PFS or outcomes were noted between open and minimally invasive methods (P=0.76). Patients who underwent BTL prior to diagnosis were found to have a recurrence rate of 28% vs. 11% in patients without history of BTL (P = 0.03). A multivariate model incorporating known risk factors for recurrence, including use of radiation, chemotherapy, depth of invasion, and LVSI, confirmed that BTL remained a significant predictor of recurrence (OR 3.18; 95% CI 1.02-9.96, P = 0.046). No differences in progression free survival were noted between patients who underwent minimally invasive vs. open surgeries in patients with stage I UPSC. However, BTL does not appear to be protective against extra-uterine spread and may change the presenting stage of biologically more aggressive tumors.

Clinical and pathologic analyses of 28 cases of uterine papillary serous carcinomas

To analyze the clinico-pathological characteristics, prognostic factors and the rational therapy for the uterine papillary serous carcinoma (UPSC). Thirty-three cases of UPSC were treated in our hospital between January 1996 and December 2005. The clinico-pathologic characteristics, treatment and prognosis were retrospectively analyzed. The three-year overall survival for patients with stage I, III and IV was 77.4%, 53.3% and 12.1%, respectively. Patients with late stages and deep myometrial invasion were associated with a worse prognosis by univariate analysis (P < 0.05), while in a multivariate analysis only late stages and poor differentiation were associated with a poor prognosis (P < 0.05). The prognosis of patients in late stages treated with postoperative chemotherapy was significantly better than those without chemotherapy (P = 0.014). Most UPSC patients are in late stages at diagnosis. They often have extra-uterine metastasis and have a poor prognosis. Complete surgical staging is recommended, and postoperative chemotherapy seems to improve the prognosis.

The Risk of Subsequent Malignancies in Women With Uterine Papillary Serous or Clear Cell Endometrial Cancers

Type II endometrial cancers include uterine papillary serous carcinoma (UPSC) and clear cell endometrial cancer (CC). Given their relative rarity, aggressive nature, and poor prognosis, little is known about the risk of subsequent malignancies at other sites. Our objective was to determine if women with UPSC or CC are at increased risk of subsequent malignancies.Type II endometrial cancers include uterine papillary serous carcinoma (UPSC) and clear cell endometrial cancer (CC). Given their relative rarity, aggressive nature, and poor prognosis, little is known about the risk of subsequent malignancies at other sites. Our objective was to determine if women with UPSC or CC are at increased risk of subsequent malignancies. Women diagnosed with UPSC or CC were identified from the SEER (Surveillance Epidemiology and End Results) Program from 1973 to 2005. Cases with a second gynecologic malignancy were excluded. Using SEER*Stat software, standardized incidence ratios (SIRs) of subsequent malignancies were calculated. A total of 8045 and 1740 patients were diagnosed with UPSC and CC, respectively. Four hundred sixty-one (5.7%) of the UPSC cases were diagnosed with at least 1 additional nongynecologic malignancy. Significant associations were found with the following malignancies: the renal pelvis, soft-tissue sarcomas, acute myeloid leukemia, the bladder, and colon. Seventy-eight CC cases (4.5%) were diagnosed with at least 1 additional malignancy. In comparison with the baseline population risk, there was no statistically significant increased risk of any subsequent malignancy with a primary diagnosis of CC. This is the first large population-based analysis of second primary malignancies after type II endometrial cancers. Uterine papillary serous carcinoma is associated with increased risks of certain subsequent malignancies, and providers should be aware of these when following up patients with this diagnosis, especially those with stage I disease. In contrast, no such associations were found with CC in this cohort.

Pure Compared With Mixed Serous Endometrial Carcinoma

To analyze whether mixed compared with pure uterine papillary serous carcinoma histology affects clinical outcome, and to assess uterine papillary serous carcinoma for its association with the precursor lesion endometrial intraepithelial carcinoma. A multi-institution observational study of stage I-IV uterine papillary serous carcinoma patients was performed. Histopathologic slides were reviewed by four expert pathologists, with determination of the percentage serous histology within each tumor. The pre-existent endometrium was evaluated for the presence of endometrial intraepithelial carcinoma. We included 108 uterine papillary serous carcinoma patients. Fifty-eight patients had mixed and 50 patients had pure uterine papillary serous carcinoma histology. On multivariable analysis, advanced International Federation of Gynecology and Obstetrics (FIGO) stage (hazard ratio [HR] 3.15, 95% confidence interval [CI] 1.57-6.32), mixed uterine papillary serous carcinoma histology (HR 0.35, 95% CI 0.19-0.66), and lymphovascular space invasion (HR 2.10, 95% CI 1.07-4.16) were significantly associated with recurrence. International Federation of Gynecology and Obstetrics stage (HR 4.67, 95% CI 2.25-9.70) and mixed uterine papillary serous carcinoma histology (HR 0.39, 95% CI 0.20-0.76) were significantly and independently associated with survival. Endometrial intraepithelial carcinoma was identified in 83.9% of all cases, with no significant difference between mixed and pure uterine papillary serous carcinoma patients. Atrophic or weakly proliferative endometrium was found in 90.7% of pure uterine papillary serous carcinoma cases, whereas hyperplastic endometrium with atypia was more commonly found in 34.7% of mixed carcinoma patients with uterine papillary serous carcinoma (P=.004). Pure uterine papillary serous carcinoma histology and FIGO stage are the most important risk factors for recurrence and survival in patients with uterine papillary serous carcinoma. Adjusted for covariates, patients with pure uterine papillary serous carcinoma had a 2.9-times greater risk for recurrence and a 2.6-times higher risk of death compared with patients with mixed uterine papillary serous carcinoma. Furthermore, endometrial intraepithelial carcinoma was equally found among pure and mixed uterine papillary serous carcinoma cases, whereas the nonneoplastic endometrium was atrophic or weakly proliferative in pure uterine papillary serous carcinoma cases compared with more hyperplastic endometrium with atypia in mixed uterine papillary serous carcinoma cases.

Clinicopathologic study on 61 cases of uterine papillary serous carcinoma with or without adjuvant therapy

To study the clinicopathologic features of uterine papillary serous carcinoma (UPSC) and the roles of adjuvant therapy. Sixty-one cases of UPSC with operation done and followed up for a period of 4 to 9 years were enrolled into the study. The histology of slides specimens were reviewed and immunohistochemical study was performed. The follow-up and survival data were analyzed. All of the 61 patients were post-menopausal, with a median age of 68 years. The clinical presentations included abnormal vaginal bleeding, abdominal symptoms and abnormal Pap smears. The median size of the tumors was 7.5 cm (range=1.2 to 14.8 cm). There were 27.9% cases in FIGO stage I (8.2% in stage IA, 14.8% in stage IB and 4.9% in stage IC), 9.8% in stage II, 32.8% in stage III and 29.5% in FIGO stage IV. The histologic features were similar to those of the ovarian counterpart, with tumor cells containing the high-grade nuclei and arranged in complex papillae. Psammoma bodies were identified in 24.6% of the cases. Immunohistochemical study showed that the tumor cells demonstrated diffuse and strong nuclear staining for p53 and Ki-67. They were negative for estrogen receptor and progesterone receptor. Fifteen of the 61 cases (24.6%) showed no evidence of myometrial invasion. However, ten of the 15 cases had extrauterine disease, with peritoneal (6/15) and nodal (9/15) involvement. Tumors with deep myometrial invasion, lymphovascular permeation and nodal metastasis were associated with worse prognosis by univariate analysis. Fifty-six patients received adjuvant therapy. The number of patients receiving adjuvant chemotherapy alone, adjuvant radiotherapy alone and combined adjuvant chemotherapy/radiotherapy were 42, 24 and 10, respectively. The median survivals of the chemotherapy group and non-chemotherapy group (with or without radiotherapy) were 66.4 months and 32.8 months, respectively. UPSC has distinctive clinical and pathologic features. The tumor stage, lymph node status, lymphovascular permeation and depth of myometrial invasion were important prognostic factors. Adjuvant chemotherapy for stage III/IV tumors or recurrent UPSC may have survival benefit.

A review of the pathology and management of uterine papillary serous carcinoma and correlation with outcome

Uterine papillary serous carcinoma (UPSC) accounts for 10% of endometrial carcinomas but a higher proportion of deaths due to its aggressive nature and poor response to chemotherapy and radiotherapy. In order to add to the knowledge of UPSC in the literature and to review our local practices, we examined the pathology, medical records, and management of all cases of UPSC (67 patients) treated in South East Scotland over a 10-year period and also evaluated the prognostic significance of the percentage of UPSC in endometrial pipelle and hysterectomy specimens. Although only 63% of initial diagnostic biopsies were reported to contain UPSC, rereview of the cases revealed UPSC in 98.5% of the preoperative biopsies. The percentage of UPSC in the tumors did not affect the outcome. Stage, positive omentum, and treatment with external-beam +/- intracavitary radiotherapy were significantly correlated with overall survival and progression-free survival by univariate analysis, but only stage (P < 0.01) was correlated with outcome on multivariate analysis. Chemotherapy did not affect outcome. UPSC may be difficult to diagnose in preoperative biopsies, particularly when present as part of a mixed tumor. Even a small percentage of UPSC in a diagnostic biopsy or hysterectomy specimen is correlated with a poor prognosis. This study emphasizes the need of a cooperative, prospective study on this distinct uterine carcinoma.

A review of the pathology and management of uterine papillary serous carcinoma and correlation with outcome

Uterine papillary serous carcinoma (UPSC) accounts for 10% of endometrial carcinomas but a higher proportion of deaths due to its aggressive nature and poor response to chemotherapy and radiotherapy. In order to add to the knowledge of UPSC in the literature and to review our local practices, we examined the pathology, medical records, and management of all cases of UPSC (67 patients) treated in South East Scotland over a 10-year period and also evaluated the prognostic significance of the percentage of UPSC in endometrial pipelle and hysterectomy specimens. Although only 63% of initial diagnostic biopsies were reported to contain UPSC, rereview of the cases revealed UPSC in 98.5% of the preoperative biopsies. The percentage of UPSC in the tumors did not affect the outcome. Stage, positive omentum, and treatment with external-beam +/− intracavitary radiotherapy were significantly correlated with overall survival and progression-free survival by univariate analysis, but only stage (P &lt; 0.01) was correlated with outcome on multivariate analysis. Chemotherapy did not affect outcome. UPSC may be difficult to diagnose in preoperative biopsies, particularly when present as part of a mixed tumor. Even a small percentage of UPSC in a diagnostic biopsy or hysterectomy specimen is correlated with a poor prognosis. This study emphasizes the need of a cooperative, prospective study on this distinct uterine carcinoma.

Papillary serous carcinoma—A less radio-sensitive subtype of endometrial cancer

Objective. To explore factors that determine the response of endometrial cancer to radiation therapy. Such factors may influence treatment outcome and yield predictive information about individual patients and their tumors. Methods. A retrospective study of the complete pathologic response (pCR) rates in the hysterectomy specimens of patients, who had undergone pre-operative radiotherapy for ≥ Stage II biopsy-proven endometrial carcinoma, was performed. 62 patient records were reviewed with respect to patient characteristics, tumor stage, histological grade and subtype, radiation technique and dose, and presence or absence of pCR in the post-operative hysterectomy specimen. Results. 24 of 62 specimens exhibited a pCR. The only significant factor with respect to pCR was presence of uterine papillary serous carcinoma (UPSC). None of the seven cases of UPSC displayed a pCR ( P = 0.036 Fischer's exact test), despite not differing from the non-UPSC cases in any other tumor, treatment, or patient factors. No factors were found that separated non-UPSC cases with a pCR from those without. Conclusions. These data suggest an intrinsic radioresistance within UPSC, which may have implications for future treatment strategies. UPSC has documented genetic aberrations that may account for this, although its true radiosensitivity has yet to be quantitated directly. Future studies should focus on the molecular basis of its response to radiation. The reasons for the heterogeneous response of non-UPSC has yet to be elucidated and should also be investigated.

P27 and Cyclin D1 Abnormalities in Uterine Papillary Serous Carcinoma

Objective. The expression status of p27 and cyclin D1 was examined in 21 uterine papillary serous carcinoma (UPSC) specimens to determine the role of these genes in the development of this disease. The status of p53, p16, Rb, and K-ras was also determined in these tissues so that a marker profile for UPSC could be compared with the published marker profile for other forms of endometrial and ovarian cancer.Methods. Immunohistochemistry was performed on 21 UPSC tissue sections to determine the expression status of p27, cyclin D1, p53, p16, and Rb. K-ras mutations were identified by restriction fragment length polymorphism analysis of DNA isolated from the UPSC sections.Results. All specimens displayed at least one molecular abnormality. A high incidence of p27 alterations were observed, with reduced p27 expression measured in 16 of 21 (76%) tumors, followed by p53 alterations observed in 13 of 21 (62%) tumors. The p27 abnormalities occur at an early stage of the disease, with 63% (5/8) of Stage I cases displaying reduced p27 expression. Cyclin D1 overexpression was observed in 4 of 21 (19%) specimens, whereas p16, Rb, and K-ras abnormalities were each observed in 2 of 21 specimens (10%). Both K-ras mutations were at codon 12. The p16 and Rb abnormalities coexisted in the same specimens.Conclusion. UPSC tumors display a high incidence of p27 abnormalities, suggesting that p27 abnormalities play an important role in the development of this disease. Our results also indicate that cyclin D1 overexpression is involved in the development of a small number of UPSC cases. A comparison of our results with reports by other authors suggests that UPSC shares molecular marker alterations with both ovarian cancer and endometrioid adenocarcinoma.

Management of Aggressive Histologic Variants of Endometrial Carcinoma at the Tom Baker Cancer Centre between 1984 and 1994

Objective. The aim of this study was to determine the patient characteristics and outcome of patients with aggressive histologic variants (AV) of endometrial carcinoma, including uterine papillary serous carcinoma (UPSC), uterine clear cell carcinoma (UCCC), and mixed type.Methods and materials. All cases with AV histological type of endometrial carcinoma from January 1984 to December 1994 at the Tom Baker Cancer Centre were identified using the Alberta Cancer Registry. Relevant data from the charts of these patients were entered into a study database (Microsoft Excel) and analyzed for presentation, demography, treatment parameters, and outcome of treatment. All pathology was reviewed at the time of diagnosis. Statistical analysis was performed using the S-plus statistics computer program. Univariate and multivariate analyses were used to assess independent prognostic factors using the Cox proportional hazards model.Results. A total of 103 patients with AV histological type were identified and analyzed; there were 61, 31, and 11 cases of UPSC, CCC, and mixed tumors, respectively. Sixty-three patients had Stage I, 11 had Stage II, 15 had Stage III, and 14 had Stage IV disease. The median age of patients was 67 years with a range of 36 to 86 years. Median follow-up was 60 months with a range of 36 to 156 months. The Cox proportional hazards model showed that lymphvascular space invasion and stage are the two independent prognostic factors affecting recurrence and survival. Forty six percent of all cases underwent surgery alone, 39% underwent treatment which included pelvic RT, and 17% underwent treatment which included chemotherapy. Pelvic recurrence was reduced significantly by radiotherapy in Stages I, II, and III (19% recurrence with no RT vs 7% recurrence with RT, P < 0.005). Chemotherapy improved overall survival, but made little difference in distant relapse rates.Conclusions. Stage Ia cases treated by surgery alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. Patients with Ib, Ic, II, and III have significantly lower pelvic failure rates if treated with pelvic radiation, but still have a high distant failure rate. Systemic therapy did not significantly improve distant relapse-free survival, but did extend overall survival. Stage IV patients usually died within 6 months with a few responding to systemic chemotherapy. These results suggest that there is a need for randomized trials for these patients.

Peritoneal Cytology in Uterine Papillary Serous Carcinoma

To highlight the significance of positive peritoneal cytology in uterine papillary serous carcinoma (UPSC). Seventeen consecutive UPSC cases with peritoneal cytology from 1993 to 1997 were reviewed and compared with the original cytologic diagnosis and extent of tumor involvement in tissues. Of the 17 post-menopausal women with UPSC, 11 had early-stage tumors (clinical stage I and II); three cases (27%) with positive peritoneal cytology were upgraded from at least International Federation of Gynecologists and Obstetricians stage IA to IIIA. No change in surgical stage was noted in four of six (67%) advanced cases with positive peritoneal cytology. The review diagnoses of peritoneal cytology did not differ from the original diagnoses. The features of UPSC in peritoneal cytology are those of a high grade malignancy and may be shared by tumors with similar histology from other sites. The malignant features are readily identified, but the site of origin may not be completely ensured. Positive peritoneal cytology upgrades the surgical stage of early-stage UPSC cases and helps with prognostication and treatment. One case with positive washings but without residual tumor probably represented early spread and/or multicentric origin of the tumor.

P53 immunoreactivity in endometrial metaplasia with dysfunctional uterine bleeding.

Overexpression of p53 has been reported in endometrial carcinomas, especially in uterine papillary serous carcinoma (UPSC), to correlate with worse prognosis. Endometrial metaplasia is commonly encountered in patients with dysfunctional uterine bleeding (DUB) and may on occasion be difficult to distinguish from atypical endometrial hyperplasia or carcinoma on biopsies. The present study was initiated in the belief that metaplastic tissue might not show overexpression of p53 and would thus help to distinguish it from carcinomas of non-endometrioid histology. Paraffin-embedded tissue of endometrial biopsies with papillary metaplasia (22 cases), tubal metaplasia (five cases) and eosinophilic meta-plasia (seven cases) from patients with DUB were immunostained for p53 immunoreactivity. No evidence of hyperplasia was noted in any of the cases selected for the study. Twenty-eight cases of UPSC were included for comparison. Our study showed p53 overexpression in 25 of 28 (89%) UPSC. Weak and heterogeneous p53 immunoreactivity was present in 10 of 22 (45%) papillary metaplasias, four of five (80%) tubal metaplasias and four of seven (57%) eosinophilic metaplasias. Follow-up of 16-45 (median 32) months was unremarkable except for one patient with eosinophilic metaplasia who had simple endometrial hyperplasia in subsequent biopsy. The presence of weak and heterogeneous p53 immunoreactivity in metaplastic endometrium is unexpected and might be a consequence of DNA damage. Intense, diffuse and homogeneous p53 staining favours carcinoma.

P53 Protein Overexpression: A Strong Prognostic Factor in Uterine Papillary Serous Carcinoma

Uterine papillary serous carcinoma (UPSC) is an uncommon but aggressive type of endometrial cancer associated with rapid progression of disease and poor prognosis. We investigated 23 cases of UPSC. p53 expression was studied in archival paraffin-embedded tissue by immunohistochemistry. Eleven tumors (47.8%) showed p53 overexpression whereas 12 tumors (52.2%) were p53 negative. One of 8 stage I/II (12.5%) and 10/15 stage III/IV (66.6%) tumors revealed p53 staining (P= 0.027). The median overall survival was 43.3 months. Patients with advanced-stage (III, IV) disease had a 5-year overall survival probability (5-year OS%) of 24% compared to 100% in those in stages I and II (log-rank,P= 0.018). Myometrial invasion, lymphatic space invasion, or lymph node involvement did not correlate with the 5-year OS of these patients. Patients whose tumors overexpressed p53 had a significantly shorter survival than those whose tumors did not (P= 0.033). This study confirms the influence of p53 overexpression on survival in UPSC patients.