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

Knowledge and attitudes towards clinical trials among women with ovarian cancer: results of the ACTO study

Background Despite several initiatives by research groups, regulatory authorities, and scientific associations to engage citizens/patients in clinical research, there are still obstacles to participation. Among the main discouraging aspects are incomplete understanding of the concepts related to a clinical trial, and the scant, sometimes confused, explanations given. This observational, cross-sectional multicenter study investigated knowledge, attitudes and trust in clinical research. We conducted a survey among women with ovarian cancer at their first follow-up visit or first therapy session, treated in centers belonging to the Mario Negri Gynecologic Oncology (MaNGO) and Multicenter Italian Trials in Ovarian Cancer (MITO) groups. A questionnaire on knowledge, attitudes and experience was assembled ad hoc after a literature review and a validation process involving patients of the Alliance against Ovarian Cancer (ACTO). Results From 25 centers 348 questionnaire were collected; 73.5% of responders were 56 years or older, 54.8% had a high level of education, more than 80% had no experience of trial participation. Among participants 59% knew what clinical trials were and 71% what informed consent was. However, more than half did not know the meaning of the term randomization. More than half (56%) were in favor of participating in a clinical trial, but 35% were not certain. Almost all responders acknowledged the doctor's importance in decision-making. Patients' associations were recognized as having a powerful role in the design and planning of clinical trials. Conclusions This study helps depict the knowledge and attitudes of women with ovarian cancer in relation to clinical trials, suggesting measures aimed at improving trial "culture", literacy and compliance, and fresh ways of communication between doctors and patients

Radioguided sentinel limphnode detection in vulvar cancer

Lymph node status is the most important prognostic factor in vulvar cancer. Histologically, sentinel nodes may be representative of the status of the other regional nodes. Identification and histopathologic evaluation of sentinel nodes could then have a significant impact on clinical management and surgery. The aim of this study was to evaluate the feasibility and diagnostic accuracy of sentinel lymph node detection by preoperative lymphoscintigraphy with technetium-99 m-labeled nanocolloid, followed by radioguided intraoperative detection. Nine patients with stage T1, N0, M0, and 11 patients with stage T2, N0, M0 squamous cell carcinoma of the vulva were included in the study. Only three cases had lesions exceeding 3.5 cm in diameter. Sentinel nodes were detected in 100% of cases. A total of 30 inguino-femoral lymphadenectomies were performed, with a mean of 10 surgically removed nodes. Histological examination revealed 17 true negative sentinel nodes, 2 true positive, and 1 false negative. In our case series, sentinel lymph node detection had a 95% diagnostic accuracy, with only one false negative. Based on literature evidence, the sentinel node procedure is feasible and reliable in vulvar cancer; however, the value of sentinel node dissection in the treatment of early-stage vulvar cancer still needs to be confirmed

P16INK4a overexpression independent of Human Papilloma Virus (HPV) infection in rare subtypes of endometrial carcinomas

Abstract In the current study, we evaluated p16 expression in rare subtypes of endometrial carcinomas, whose HPV status has been previously examined in order to establish the role of this protein in their pathogenesis. These rare subtypes of endometrial carcinomas are primary squamous endometrial carcinoma (ESCC), endometrial mucinous microglandular adenocarcinoma (EMMA), and endometrial transitional cell carcinoma (ETCC). All tissues, obtained at the time of hysterectomy, were fixed in 10% phosphate-buffered formalin and embedded in paraffin. Serial sections were made for hematoxylin and eosin staining and for immunohistochemistry. Although a previous PCR study has demonstrated that none of these neoplasms showed any signal for HPV DNA, these malignancies did display immunoreactivity for P16INK4a. In ESCC, P16INK4a immunoreactivity was diffuse in 100% of neoplastic cells. In two cases of EMMA, positivity for P16INK4a was zonal. In ETCC, scattered cells were positive for P16INK4a protein. These findings suggest that alteration of p16 could play an etiologic role, without any association to HPV infections, in these rare endometrial carcinomas. However, in our view, other cases of these rare malignancies should be investigated in order to confirm this hypothesis

Vulvar acantholytic squamous carcinoma: a case report with immunohistochemical and molecular study.

Abstract Acantholytic carcinoma is a subtype of squamous carcinoma, characterized by tubular and alveolar formations as a consequence of the acantholysis. We report a case of vulvar squamous acantholytic carcinoma (VSAC) in a 69-year-old woman, who was admitted to our institution for vulvar pruritus and the presence of a large, bilateral, exophytic, and ulcerated lesion, measuring 7 x 8 cm. The patient had never received vulvar or pelvic radiation therapy. Pathological examination with an immunohistochemical study showed features of VSAC and high p16(INK4a) protein expression. Molecular study by polymerase chain reaction amplification of DNA tumor revealed a weakly positive signal for human papillomavirus. In conclusion, our case, which is the first case of VSAC with polymerase chain reaction analysis and immunohistochemical expression of p16(INK4a) protein, suggested that this neoplasm could be related to human papillomavirus infection

Psychophysiological Adjustment to Ovarian Cancer: Preliminary Study on Italian Women Condition

This study aimed to evaluate the psychological and physiological adjustment in a sample of Ovarian Cancer survivors. For all we know, this is the first time that such analysis has been performed in Italy. We assessed psychological adjustment along with physiological adjustment, measured through the basal Heart Rate Variability at rest. We assessed 38 women overall, aged 29–80 years, in follow up for ovarian cancer. Each participant filled a psycho-oncological record, Multidimensional Scale of Perceived Social Support, Derridford Appearance Scale-59, Mental Adjustment to Cancer and EORTC Quality of Life Questionnaire LQ-30 Version 3.0. For each participant, we recorded Heart Rate Variability (5 min). These women have shown a high rate of perceived general social support (Me = 5.93) but they seem to have some general concern about their appearance (Me = 85.97, SD = 24.4). They have also shown a rather good total Quality of Life (QL2 Me = 66.32) with specific difficulties in emotional functioning (EF; Me = 69.19). Heart Rate Variability values, however, were lower of nearly 50% when compared to normative values. These women, then, seem to drag concerns and difficulties, in particular linked to the acceptance of their condition. Surprisingly enough, the best adjustment in these women seems to be related to the worst starting conditions. It is possible to suggest that the extremely negative conditions force these women to face cancer openly, as well as their condition of cancer survivors, pushing them “moving on” more than “trying to get back”

Endometrial mucinous microglandular adenocarcinoma: morphologic, immunohistochemical features and emphasis in the HPV status

ABSTRACT 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 peculiarhormonal situation