Prognostic role of mesenteric lymph nodes involvement in patients undergoing posterior pelvic exenteration during radical or supra-radical surgery for advanced ovarian cancer.

PURPOSE: The aim of this retrospective study is to analyze the prognostic role and the practical implication of mesenteric lymph nodes (MLN) involvements in advanced ovarian cancer (AOC). METHODS: A total of 429 patients with AOC underwent surgery between December 2007 and May 2017. We included in the study 83 patients who had primary (PDS) or interval debulking surgery (IDS) for AOC with bowel resection. Numbers, characteristics and surgical implication of MLN involvement were considered. RESULTS: Eighty-three patients were submitted to bowel resection during cytoreduction for AOC. Sixty-seven patients (80.7%) underwent primary debulking surgery (PDS). Sixteen patients (19.3%) experienced interval debulking surgery (IDS). 43 cases (51.8%) showed MLN involvement. A statistic correlation between positive MLN and pelvic lymph nodes (PLN) (p = 0.084), aortic lymph nodes (ALN) (p = 0.008) and bowel infiltration deeper than serosa (p = 0.043) was found. A longer overall survival (OS) and disease-free survival was observed in case of negative MLN in the first 20 months of follow-up. No statistical differences between positive and negative MLN in terms of operative complication, morbidity, Ca-125, type of surgery (radical vs supra-radical), length and site of bowel resection, residual disease and site of recurrence were observed. CONCLUSIONS: An important correlation between positive MLN, ALN and PLN was detected; these results suggest a lymphatic spread of epithelial AOC similar to that of primary bowel cancer. The absence of residual disease after surgery is an independent prognostic factor; to achieve this result should be recommended a radical bowel resection during debulking surgery for AOC with bowel involvement.

Secondary analyses from a randomized clinical trial: age as the key prognostic factor in endometrial carcinoma.

OBJECTIVE: The purpose of this study was to explore in greater depth the outcomes of the Italian randomized trial investigating the role of pelvic lymphadenectomy in clinical early stage endometrial cancer. In the attempt to identify the patients with poorer prognosis, the impact of age and body mass index were also thoroughly investigated by cancer-specific survival (CSS) analyses. STUDY DESIGN: Survival outcomes of trial patients were analyzed in relation to age (≤65 years and >65 years) in the 2 arms (lymphadenectomy and no lymphadenectomy) and in the whole population of the trial. RESULTS: Univariate and multivariable analyses of CSS and overall survival (OS) of patients showed that age >65 years is a strong independent poor prognostic factor (5-y OS 92.1% and 78.4% in ≤65 years and >65 years patients, respectively, P < .0001; 5-y CSS 93.8% and 83.5% in ≤65 years and >65 years patients, respectively, P = .003). Among women ≤65 years, node negative patients had 94.4% 5-y OS and 96.3% 5-y CSS vs 74.3% 5-y OS and 74.3% 5-y CSS for node positive patients (P = .009 and P = .002, respectively), while among women >65 y, node negative patients had 75.7% 5-y OS and 83.6% 5-y CSS vs 74.1% 5-y OS and 83.3% 5-y CSS for node positive patients (P = .55 and P = .58, respectively). Univariate and multivariable survival analyses in the whole trial population showed that older age, and higher tumor grade and stage were significantly associated to a worse prognosis. CONCLUSION: Older women faced an intrinsic poorer survival whether or not they underwent lymphadenectomy, and, unexpectedly, irrespective of the presence of nodal metastasis. Only in older patients was obesity (body mass index >30) significantly associated with scarce prognosis.

A phase 2 multicenter study of irinotecan and cisplatinum as neoadjuvant treatment in patients with locally advanced cervical cancer.

HYPOTHESIS: To evaluate efficacy and safety of a neoadjuvant treatment with irinotecan and cisplatin [cis-diamminedichloroplatinum(II); CDDP] in patients with locally advanced cervical cancer. METHODS: A phase 2 study was conducted at 13 centers located in Italy. Eighty-seven were enrolled between 2000 and 2003. Patients received irinotecan 175 mg/m2 on day 1 every 3 weeks followed by CDDP 80 mg/m2. Each patient was to receive 3 cycles of treatment. Tumor response was to be evaluated by magnetic resonance imaging 3 weeks after the end of the third cycle. At the end of therapy, all patients were to be examined for radical surgery. RESULTS: Of 71 patients included in the primary analysis, 9 (12.7%) showed a complete response; and 43 (60.6%), a partial response for an overall response rate of 73.2% (95% confidence interval [CI], 61.4%-83.1%). Complete pathological responses were observed in 13.6% of the patients (95% CI, 7.0%-23.0%). Overall survival rate at 4 years was 87.0% (95% CI, 79.5%-94.5%).There were no study-related deaths. Most common adverse events were alopecia in 76 patients (87.4%) and gastrointestinal disorders in 79 patients (90.8%). Serious adverse events were vomiting in 18 patients (20.7%), nausea in 14 (16.1%), diarrhea in 8 (9.2%), and neutropenia in 50 (57.5%). A total of 3 patients (3.4%) were discontinued from the study owing to the occurrence of 1 or more serious adverse event. CONCLUSIONS: Irinotecan and CDDP as neoadjuvant chemotherapy in locally advanced cervical cancer showed a promising response rate. These data warrant confirmation with a phase 3 study.

Randomised prospective study of abdominal wall closure in patients with gynaecological cancer.

BACKGROUND: Median laparotomy is the most common approach to the abdominopelvic cavity in patients with gynaecological tumours. AIMS: The primary endpoint of the study was to evaluate the onset of incisional hernia. The secondary endpoint was to evaluate the onset of infection, wound dehiscence, wound infection, and scar pain during the post-operative period. METHODS: A total of 191 patients were eligible for the study. They were divided into three groups. Group A underwent en bloc closure of the peritoneum and fascia with Premilene suture, Group B en bloc closure of the peritoneum and fascia with Polydioxanone suture, and Group C separate closure of the peritoneum and fascia with single stitches of Ethibond suture. Statistical analysis was performed using the Statistical Software Package for Social Sciences 12.0. RESULTS: Group A and Group B comprised 63 patients, and Group C included 65 patients. The three groups proved homogeneous on statistical analysis (P > 0.05). The statistical analysis did not reveal significant differences between the different suture types and techniques with respect to the incidence of incisional hernia (P > 0.05). CONCLUSION: In our study, the incidence of incisional hernia was 8%. Randomised patients were homogeneous for sample size and risk factors. No significant differences were found between suture types or techniques. Currently, there is no suture material or technique that can be considered superior to others. When possible, we believe that the best way to prevent incisional hernia is to preserve the integrity of the abdominal wall using minimally invasive techniques.

Human papilloma virus (HPV) status, p16INK4a, and p53 overexpression in epithelial malignant and borderline ovarian neoplasms.

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer.

Postmenopausal status, hypertension and obesity as risk factors for malignant transformation in endometrial polyps.

OBJECTIVES: We analyzed clinical data and pathological features of six cases of malignant endometrial polyps, to compare these with other examples reported in literature and to define the features of endometrial cancer arising in polyps. Moreover, to clarify the mechanisms of carcinogenesis in malignant endometrial polyps we examined the expression of cyclooxygenase-2 (COX-2), P53 and Ki 67 and their relationships with clinicopathologic characteristics. METHODS: The surgical pathology files of the Pathology Department of Parma University were searched for cases of endometrial polyps with nests of endometrial carcinomas, from the years 2002-2005. Clinical records, histological slides of endometrial curetting, hysterectomy with salpingo-oophorectomy specimens and pelvic lymph nodes were reviewed in each case. The main pathological features analyzed were histological types of endometrial cancer and the stage of development of neoplasm. The presence of other malignancies in the genital tract were also considered. Immunohistochemical staining was done using antibodies COX-2, p53 and Ki 67. RESULTS: In our study, all malignant endometrial polyps had been detected in postmenopausal women. The majority of our patients with malignant endometrial polyps had risk factors for the development of endometrial carcinoma such as hypertension, obesity and unopposed estrogen therapy. Unlike other studies, no patients had a history of previous breast carcinoma and Tamoxifen treatment. The most common subtypes of endometrial carcinoma in malignant polyps are endometrioid carcinoma and serous papillary carcinoma. Endometrial carcinoma arising in endometrial polyps is an early endometrial carcinoma with good prognosis, except for papillary serous carcinoma, which can be associated with multiple omental involvement, despite low stage of development in the uterus. Immunohistochemical study showed that COX-2 expression was found in cytoplasm of tumor cells and this was elevated in all cases, independently of the grade and the stage of development of the malignancy, histological subtype and deep invasion of myometrium. P53 and Ki 67 expression, detected in the nuclei of neoplastic cells, was not correlated with COX-2 immunoreactivity, but these markers were associated with more advanced stage, grading, and histologic subtypes of tumor. CONCLUSIONS: Postmenopausal status, hypertension, obesity could all be considered as risk factors for carcinomatous transformation within endometrial polyps in women without a history of breast carcinoma and Tamoxifen treatment. However, our series is small (only six cases considered) and further studies are necessary to confirm this hypothesis. In the current study, immunohistochemical data reveal that COX-2 expression may be associated with the carcinogenesis in endometrial carcinomas arising in endometrial polyps, but this antibody is not correlated with tumor aggressiveness, P53 and Ki 67 expression. P53 and Ki 67 overexpression, instead, are associated with advanced stage, histologic subtype and deep myometrial invasion of neoplasm.

Paclitaxel 175 or 225 mg per meters squared with carboplatin in advanced ovarian cancer: a randomized trial.

PURPOSE: To analyze the effect of different doses of paclitaxel with fixed doses of carboplatin in the treatment of ovarian cancer. PATIENTS AND METHODS: Patients with histologically confirmed epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stages IIB to IV, were eligible for this randomized, multicenter study. Women were randomly assigned to treatment with (1) carboplatin at the dose (in milligrams) corresponding to the following formula: target area under the free carboplatin plasma concentration versus time curve (AUC) = 6 x (glomerular filtration rate + 25) mg/m(2) (AUC6) plus paclitaxel 175 mg/m(2) for six cycles every 21 days or (2) carboplatin AUC6 plus paclitaxel 225 mg/m(2) for six cycles every 21 days. A total of 502 women entered the study. RESULTS: Pathologic complete response was documented in 132 patients (63.8%) in the 175 mg/m(2) group and in 127 cases (55.7%) in the 225 mg/m(2) group (chi(2) P =.090). The 4-year progression-free survival rate was 41.5% (SE = 3.5) in the 175-mg group and 39.2% (SE = 3.5) in the 225-mg group. The corresponding 4-year survival rates were 46.2% (based on 115 deaths) and 47.3% (based on 113 deaths), respectively. CONCLUSION: This randomized trial suggests that paclitaxel 175 mg/m(2) plus carboplatin AUC6 is the schedule with a more favorable profile than paclitaxel 225 mg/m(2) plus carboplatin AUC6.

Endometrial carcinoma metastatic to the vulva: a case report and review of the literature.

In this paper, we report a new case of metastatic endometrial carcinoma to the vulva and describe the clinical and pathological features. We reviewed the literature to determine the frequency and to evaluate the prognostic significance of this rare disease. Moreover, we discuss the criteria for the differential diagnosis of endometrial carcinoma metastatic to the vulva, the primary vulvar adenocarcinomas, and other metastatic adenocarcinomas. The patient, previously diagnosed to have endometrial adenocarcinoma with squamous differentiation at III C stage (according to the FIGO system) and T2N1M0 stage (according to the TNM system), presented with a small plaque on the vulvar mucosa 8 months after endometrial primary carcinoma had been diagnosed. The histological evaluation of excisional vulvar biopsy revealed a neoplasm with pathological features of endometrial carcinoma. Thus, the final diagnosis was metastatic endometrial carcinoma to the vulva. A total body computed tomography scan (CT) and an echotomography with contrast medium revealed a second metastatic lesion at the 8th segment of the liver. No other metastatic lesions developed, nor was a reduction in the size of liver metastasis observed after 3 months of hormonic treatment with progesterone. Fourteen months after the diagnosis of primary endometrial carcinoma, the patient died of disseminated metastatic lesions. In conclusion, metastatic endometrial carcinoma to the vulva, although rare, might develop and could appear within a few months after the diagnosis of primary tumor. Moreover, in the presence of metastatic endometrial carcinoma to the vulva, it is necessary to verify if other visceral metastases are present.

Endometrial cancer in patients with preoperative diagnosis of atypical endometrial hyperplasia.

OBJECTIVE: Atypical endometrial hyperplasia (AEH) has been associated with the presence of concomitant endometrial carcinoma (EC). The aim of this study is to examine the frequency of coexisting endometrial carcinoma when atypical endometrium hyperplasia was found upon biopsy. We also evaluated the influence of preoperative diagnostic techniques (pipelle and dilation and curettage (D&C)), and the value of transvaginal ultrasound in detecting unexpected tumor invasion. STUDY DESIGN: Between January 1992 and December 2003, at the Department of Obstetrics and Gynecology, University of Parma, and Policlinico S. Matteo, Pavia, 70 consecutive patients subjected to total hysterectomy with a histological diagnosis of AEH were retrospectively selected. 52/70 patients underwent vaginal hysterectomy, with bilateral salpingo-oophorectomy (BSO) whereas 18/70 had abdominal hysterectomy with BSO within 8 weeks since the diagnosis of AEH. RESULTS: We found in 30 of the 70 patients with atypical endometrial hyperplasia in the biopsy coexisting endometrial carcinoma (43%). No differences in diagnostic accuracy between the pipelle method and D&C were found. CONCLUSION: Transvaginal ultrasound was not a feasible method for predicting EC. After a follow-up of an average of 5 years there was, neither in the abdominal operated patients nor in the vaginal operated patients, a recurrence of disease.

Retzius' space haematoma after spontaneous delivery: a case report.

We report a case of a haematoma of the Retzius space after spontaneous uncomplicated delivery. In the postpartum period, the patient complained of urinary retention and pain in the hypogastric region radiating to her left hip and leg. The ultrasound examination showed the presence of 160 x 100 x 80 mm confluent solid and liquid areas with peripheral vascularization. At exploratory laparotomy a haemorrhagic infiltration was found in Retzius' space and the anterior wall of the bladder, which appeared thickened and swollen below the peritoneum. We tried to drain the haematoma, however, we failed to drain it completely because of the large blood infiltration in the bladder wall. Clinical and ultrasound follow-up examinations showed a progressive reduction of the haematoma which completely disappeared nine months later. The haemodynamic changes occurring during pregnancy and labour, associated with strong mechanical stress, seem to be among the major causative factors of haematoma formation. Moreover, the venous load in the pelvic vascular system is increased during pregnancy; a stress-induced increase in venous blood pressure might play a prominent role, especially in cases of venous ectasia, where the resistance of blood vessel walls is reduced. Intraoperative evidence seemed to suggest a haemorrhage secondary to the rupture of the venous vessels in the Santorini plexus. The rupture was probably caused by the thrust of the fetal head, associated with abnormality or fragility of the blood vessels, or by some pathologic changes occurring in the anatomical structures during pregnancy, which could not be accurately defined because of the severity and degree of the haematoma infiltration found intraoperatively.

Single-dose methotrexate for ectopic pregnancy treatment: preliminary data.

BACKGROUND AND AIM OF THE WORK: Our purpose was to evaluate the efficacy of a single-dose of MTX for ectopic pregnancy treatment in a sample of patients carefully selected according to strict inclusion criteria. METHODS: 11 patients that matched the inclusion criteria were enrolled. RESULTS: Beta-hCG at diagnosis averaged 1349 mIU/ml out of the 11 treated patients, 10 (90%) received a single dose of MTX and had a time of EP resolution averaging 27.3 days. The remaining patient received an additional dose of MTX, equal to the start dose, with a time resolution of 35 days. CONCLUSIONS: This study provides evidence of the efficacy of MTX in EP treatment, both as therapy and as a form of clinical management: the successful medical management of EP, defined as beta-hCG levels becoming negative after administration of one or more MTX doses, was obtained in all treated cases.

Small cell carcinoma of the uterine corpus: CT appearance.

We report a rare case of small-cell carcinoma of the uterine corpus. To our knowledge, this is the first radiological report. Computed tomography (CT) demonstrates a hypodense lesion within the endometrial cavity with nonhomogeneous contrast enhancement.

Preoperative transvaginal ultrasonography and intraoperative gross examination for assessing myometrial invasion by endometrial cancer.

OBJECTIVE: Endometrial cancer is the most common gynecologic malignancy. The cornerstone of treatment remains surgery according to International Federation of Gynecology and Obstetrics staging. The aim of this study was to evaluate the concordance between myometrial infiltration detected by ultrasonography and gross examination with respect to definitive histologic examination and to select a population in which lymphadenectomy could be excluded. We also evaluated the concordance for the degree of tumor differentiation between diagnostic biopsy and final histologic results. METHODS: Our study included 75 patients with International Federation of Gynecology and Obstetrics stage I endometrial cancer. We evaluated preoperative and definitive grading and myometrial infiltration detected by ultrasonography and gross examination. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the procedures under study were determined with the Bayes theorem. To determine the predictive value of preoperative transvaginal ultrasonography and intraoperative gross examination for myometrial invasion, we used a multiple logistic regression model with a statistical software package. RESULTS: Our study showed 60% concordance between biopsy and histologic results. In 80% of the cases with discordant results, the tumor was undergraded. Ultrasonography had diagnostic accuracy of 73%, whereas gross examination correctly determined myometrial invasion in 82.6% of the patients, with sensitivity of 62% and specificity of 79%. CONCLUSIONS: Preoperative transvaginal ultrasonography and macroscopic gross examination appear to be simple, fast, and reliable methods to predict in myometrial invasion in patients with a low risk for lymph node metastasis, for which lymphadenectomy can reasonably be avoided.

Role of human papillomavirus in the development of epithelial ovarian neoplasms in Italian women.

AIM: In this article, for the first time, we investigate the presence of human papillomavirus (HPV) DNA in ovarian epithelial neoplasms from a group of 71 Italian women. The follow ups of the patients with or without HPV DNA were also considered to evaluate whether HPV DNA in these tumors could be an indicator of prognosis. METHODS: HPV DNA was evaluated by polymerase chain reaction (PCR). Additionally P16 immunoreactivity was evaluated in all positive cases to demonstrate the presence of HPV. RESULTS: Only three cases out of 71 epithelial ovarian neoplasms (4.22%) in this series were weakly HPV positive. The presence of HPV DNA in these cases did not seem to be related with the type of neoplasm, their grade of differentiation, staging of development, patient's age or survival. CONCLUSION: The presence of HPV could be an expression of a latent infection. In both positive and negative HPV ovarian neoplasms, cervix showed only chronic cervicitis and no signal for HPV DNA on PCR analysis.

Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.

BACKGROUND: Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer, but the clinical impact of lymphadenectomy has not been addressed in randomized studies. We conducted a randomized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to standard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival. METHODS: From October 1, 1996, through March 31, 2006, 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were randomly assigned to undergo pelvic systematic lymphadenectomy (n = 264) or no lymphadenectomy (n = 250). Patients' clinical data, pathological tumor characteristics, and operative and early postoperative data were recorded at discharge from hospital. Late postoperative complications, adjuvant therapy, and follow-up data were collected 6 months after surgery. Survival was analyzed by use of the log-rank test and a Cox multivariable regression analysis. All statistical tests were two-sided. RESULTS: The median number of lymph nodes removed was 30 (interquartile range = 22-42) in the pelvic systematic lymphadenectomy arm and 0 (interquartile range = 0-0) in the no-lymphadenectomy arm (P < .001). Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy (81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm, P = .001). Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm (13.3% vs 3.2%, difference = 10.1%, 95% confidence interval [CI] = 5.3% to 14.9%, P < .001). At a median follow-up of 49 months, 78 events (ie, recurrence or death) had been observed and 53 patients had died. The unadjusted risks for first event and death were similar between the two arms (hazard ratio [HR] for first event = 1.10, 95% CI = 0.70 to 1.71, P = .68, and HR for death = 1.20, 95% CI = 0.70 to 2.07, P = .50). The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms (81.0% and 85.9% in the lymphadenectomy arm and 81.7% and 90.0% in the no-lymphadenectomy arm, respectively). CONCLUSION: Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging, it did not improve disease-free or overall survival.

Villoglandular adenocarcinoma of the cervix: two new cases with morphological and molecular study.

In this paper, we report 2 new cases of villoglandular papillary adenocarcinoma (VGPA) of the cervix, a rare, well-differentiated form of cervical adenocarcinoma. Both patients were without medical complications or history of oral contraceptive use and were nonsmokers. Extended hysterectomy was performed in both cases. Morphological criteria for a correct pathological diagnosis were emphasized. Immunohistochemical analysis was performed to clarify the phenotype of the neoplasms. Moreover, for the first time, we probed to establish if VGPA could be correlated to human papilloma virus (HPV) and herpes virus (HSV) types 1 and 2, using polymerase chain reaction amplification of tumoral DNA. Both neoplasms showed positivity for B72.3, Ca-125, carcinoembryonic antigen, keratin 7, and p16(INK4a) protein. Vimentin, P53, estrogen, and progesterone receptors, instead, were negative. Molecular study by polymerase chain reaction amplification of tumor DNA revealed a strong positive signal for HPV-DNA and no signal for HSV-DNA. It is reasonable to conclude that our cases of VGPA, in accordance with other examples reported in literature, are due to HPV infection. Behavioral cofactors, such as HSV infection (types 1 and 2), oral contraceptive use and smoking, involved in the pathogenesis of other cervical malignancies, can be excluded for the present cases.

Endometrial mucinous microglandular adenocarcinoma: morphologic, immunohistochemical features, and emphasis in the human papillomavirus status.

We report two cases of endometrial microglandular adenocarcinoma, a rare neoplasm, which, in its morphologic features, mimics cervical microglandular hyperplasia and mucinous proliferations of endometrium. The criteria for a correct pathological diagnosis, such as clinical, morphologic, and immunohistochemical data, are emphasized. For the first time, we probed to establish whether endometrial mucinous microglandular adenocarcinoma could be correlated to human papilloma virus (HPV) infection by using polymerase chain reaction amplification (PCR) of tumoral DNA. Similar to previous studies reported in the literature, the present lesions, occurring in postmenopausal women, immunohistochemically showed positivity for B72.3, Ca 125, CEA, Vimentin, estrogen and progesterone receptors, and negativity for p53. Molecular study by PCR amplification of tumor DNA showed no signal for HPV DNA in any of these cases; thus, this variant of endometrial carcinoma is not caused by the HPV infection, but probably by other pathogenetic mechanisms, such as an accumulation of the mutations, which arrive in old age or as the consequence of a peculiar hormonal situation.