The monoclonal antibody Ki-67, prepared by our group,3 reacts with a nuclear antigen present in proliferating cells but absent in quiescent cells. A detailed cell cycle analysis showed that the Ki-67 antigen is expressed throughout the whole cell cycle, making the antibody suitable for the determination of the growth fraction of a benign or malignant human cell subset.4 We recently showed a highly significant correlation between the proportion of Ki-67 positive cells and the histological classification of malignant nonHodgkin's lymphomas into high and low grade malignancies.5 Thus the determination of the growth Accepted for publication 9 April 1986 fraction with Ki-67 might be a new and reliable prognostic marker for these tumours.The evaluation of cell kinetic data in mammary carcinomas should also be undertaken for tumour grading, as this can provide reproducible prognostic information.This paper reports on the immunohistological determination of the growth fraction with Ki-67 in a variety of breast tumours and compares the results with conventional histological grading. Material and methodsThirty benign mammary lesions and 160 mammary carcinomas from patients attending the gynaecology clinics at the Klinikum Steglitz, and the Medical School, Hannover, were studied. There were 148 invasive ductal carcinomas, nine invasive lobular carcinomas, three medullary carcinomas and no carcinomata in situ. Cryostat sections of biopsy specimens were immunostained with monoclonal antibody

Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric viruslike particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self-assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1-and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo-controlled clinical trial has been conducted in 39 HPV16 mono-infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 lg or 250 lg) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty-six percent of the responders were also HPV16 DNA-negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine. ' 2007 Wiley-Liss, Inc.Key words: cervical cancer; clinical trial; immunization; antibody; T cell Genital infection with human papillomavirus (HPV) is one of the most common sexually transmitted diseases. Various molecular and epidemiological studies have documented a correlation between infection with ''high risk'' HPV types and premalignant or malignant tumors of the anogenital tract. 1,2 It is widely acknowledged that a causal relationship exists between persistent HPV infection and development of cervical intraepithelial neoplasia (CIN) and cervical cancer. 3,4 There are over 100 known papillomavirus types that are stratified into low and high risk, based on their association with malignant and invasive lesions. More than 95% of invasive cervical cancers are positive for HPV-DNA, mainly from HPV types 16 (50%) and 18 (20%). Moreover, HPV16 can be detected in 30270% of all HPV-positive high grade CIN patients. 5,6 The prevalence of HPV16 in other intraepithelial neoplasias is even higher, e.g., 70280% in high grade vulvar intraepithelial neoplasia. 7 Whereas for low grade CIN a high spontaneous recovery rate is observed 6,8 high grade CIN regress less often particular at higher age when lesions are more persistent. 9 Because of the potential progression of high grade CIN to invasive cancer, 10 a thorough evaluation consisting of colp...

BackgroundHuman papillomavirus (HPV) infection is a prerequisite of cervical cancer, the leading cause of cancer mortality in Ethiopian women today. Data on Ethiopian cervical HPV prevalence and genotype distribution are rare, but essential as pre-vaccine baseline data to monitor changes after initiating HPV vaccination. The objectives of this study were to assess the cervical HPV prevalence, genotype distribution and associated correlates among female hospital outpatients in rural Ethiopia.MethodsWe examined a consecutive sample of 537 women 15–64 years of age in rural Ethiopia between November and December 2006. Screening for low risk (LR) and high-risk (HR) cervical HPV infection was performed and HR positive samples were genotyped with a GP5+/6 + − and SPF10-primer based system.ResultsThe age-standardized prevalence of HPV, HPV HR and HPV LR infection was 17.3% (95% CI 14.1-20.5), 15.8% (95% CI 12.7-18.9) and 3.9% (95% CI 2.3-5.6), respectively. Among HC2 HPV HR positive infections (n = 86), the most common genotype was HPV 16 (24.4%), followed by 52 (11.6%), 56 (10.5%) and 31 (10.5%). Non-married relationship and widowhood, increasing number of lifetime sexual partners, human immunodeficiency virus infection and non-traditional housing type, but not age, were significantly associated with HR HPV infection.ConclusionsThese results on cervical HPV prevalence and genotype distribution may serve as baseline data in evaluating the impact of future HPV vaccination programmes in rural Ethiopia.Electronic supplementary materialThe online version of this article (doi:10.1186/1750-9378-9-33) contains supplementary material, which is available to authorized users.

To evaluate the expression of markers correlated with cellular senescence and DNA damage (8-hydroxy-2′-deoxy-guanosine (8-OHdG), p53, p21, APE1/Ref-1 (APE1), interleukin (IL-6 and IL-8) in placentas from healthy and pathologic pregnancies. This retrospective study considered a placental tissue micro-array containing 92 controls from different gestational ages and 158 pathological cases including preeclampsia (PE), HELLP syndrome (hemolysis, elevated liver enzymes,low platelet count), small for gestational age (SGA)fetuses, and intrauterine growth restriction (IUGR) occurringat different gestational ages. In this study, we demonstrated a significant influence of gestational age on the expression in the trophoblast of 8-OHdG, p53, p21, APE1, and IL-6. In placentas of cases affected by PE, HELLP, or IUGR, there was an increased expression of 8-OHdG, p53, APE1, and IL-6 compared to controls (only IL-8 was significantly decreased in cases). In both groups of pathology between 22- and 34-week gestation and after 34-week gestation, APE1 levels were higher in the trophoblast of women affected by hypertensive disorders of pregnancy than women carrying an IUGR fetus. The cytoplasmic expression of 8-OHdG was increased in placentas in IUGR cases compared to PE or HELLP pregnancies. In cases after 34-week gestation, p21 was higher in SGA and IUGR than in controls and late PE. Moreover, p53 was increased after 34-week gestation in IUGR pregnancies. Placentas from pathological pregnancies had an altered expression of\ud 8-OHdG, p53, p21, APE1, IL-6, and IL-8. The alterations of intracellular pathways involving these elements may be the cause or the consequence of placental dysfunction, but in any case reflect an impaired placental function, possibly due to increased aging velocity in pathologic cases

Background:The long-term results of radiotherapy in primary carcinoma of the vagina are not well defined. Patients and Methods: The treatment results of 41 patients with primary malignancies of the vagina were analyzed. The mean follow-up period was 77.3 months (2.3-404 months). The predominant histology was squamous cell carcinoma, FIGO stages I: n = 7 (17.1%), II: n = 13 (31.7%), III: n = 13 (31.7%), and IVa: n = 8 (19.5%). Radiotherapy was the primary treatment for all patients. None of the patients had undergone prior surgery for vaginal carcinoma. The majority of patients received pelvic irradiation, including treatment of the inguinal lymphatics (median dose: 50 Gy). 26 patients received additional intravaginal brachytherapy. Results: Overall, 21 patients (51.2%) achieved complete remission, 17 patients (41.5%) had partial responses, and three patients (7.3%) had no change or progressive disease. The total median survival of the analyzed patients was 41.3 months. The 1-year survival probability was 85.4%, the 5-year survival probability 40.6%, and the 10-year survival probability 27.2%. Univariate analysis revealed a survival advantage for earlier tumor stages (FIGO I and II) compared to advanced stages (FIGO III and IV), with a median survival of 58.1 months compared to 26.8 months. Treatment side effects were tolerable and easily managed. Conclusion: Definite radiotherapy is the treatment of choice for primary carcinomas of the vagina. Considering that primary malignancies of the vagina are typically diseases of the elderly, it should be noted that radiotherapy is especially well tolerated in this population. Langzeitergebnisse der Strahlentherapie beim primären VaginalkarzinomHintergrund: Die Langzeitergebnisse der Strahlentherapie beim primären Vaginalkarzinom sind nicht gut definiert. Patienten und Methodik: Die Behandlungsergebnisse von 41 Patientinnen mit primären Vaginalkarzinomen wurden analysiert. Der mittlere Nachbeobachtungszeitraum betrug 77,3 Monate (2,3-404 Monate). Histologisch lagen überwiegend Plattenepithelkarzinome vor, FIGO-Stadien I: n = 7 (17,1%), II: n = 13 (31,7%), III: n = 13 (31,7%), IVa: n = 8 (19,5%). Bei allen Patientinnen war die Strahlentherapie die primäre Behandlungsform, keine Patientin hatte sich vor Bestrahlungsbeginn einer chirurgischen Intervention unterzogen. Der Großteil der Patientinnen erhielt eine Beckenbestrahlung, welche die inguinalen Lymphbahnen einschloss (mittlere Dosis: 50 Gy). 26 Patientinnen erhielten zusätzlich eine intravaginale Brachytherapie. Ergebnisse: Insgesamt erreichten 21 Patientinnen (51,2%) eine komplette Remission, 17 Patientinnen (41,5%) wiesen eine partielle Remission auf, und drei Patientinnen (7,3%) zeigten keine Veränderung bzw. ein Fortschreiten der Erkrankung. Das Gesamtüberleben für alle Patientinnen lag im Median bei 41,3 Monaten. Die 1-Jahres-Überlebenswahrscheinlichkeit betrug 85,4%, die 5-Jahres-Überlebenswahrscheinlichkeit 40,6% und die 10-Jahres-Überlebenswahrscheinlichkeit 27,2%. Die univariate Analyse zeigte einen Überlebensvo...

No abstract

Adenoid cystic carcinoma of the Bartholin's gland has been encountered in 11 patients at the University of Michigan Medical Center since 1936. At the time of presentation the average age was 48.9 years, the lesion size was between 0.5 to 4 cm. The presenting symptoms were pain and/or pruritis associated with a solitary mass. Early in this series, excisional biopsy was used to treat eight patients. The last three patients have been treated with a radical vulvectomy and unilateral or bilateral groin lymph node dissection. Local recurrence has occurred in five patients and distant recurrence in four patients. In spite of the high recurrence rate, 5- and 10-year survival has been high with all seven evaluable patients surviving 5 and 10 years. However, adenoid cystic carcinoma of the vulva is associated with late recurrences and metastases: three patients were dead of disease at 12, 15 and 31 years after initial diagnosis.

The monoclonal antibody Ki-67 reacts with a human nuclear associated with cell proliferation that is expressed only in the G1, S, G2, and M phases of continuously cycling cells. This offers a simple opportunity to determine the growth fraction of tumors by immunostaining of fresh tissue. One hundred fifty-four invasive carcinomas of the breast were used in this study. The average number of Ki-67 positive cells was 15.3 +/- 10.1% (range, 1%-48%), whereas in 41 benign lesions of the breast only 4.4 +/- 2.6% (range, 1%-10%) of cells were positive. A correlation was found between growth fractions and histologic grading. On average, N+ tumors with less than four positive lymph nodes had a significantly higher growth fraction (20.4 +/- 14.2%) than N0 tumors (13.0 +/- 9.2%), whereas N+ tumors with more than three lymph node metastases had only 17.3 +/- 3.6% Ki-67 positive cells. This method yielded similar results to those obtained by other researchers through the use of flow cytometry and thymidine labeling. Determination of growth fractions by Ki-67 is suitable for routine use and may be useful in prognosis and in the selection of patients for various treatment modalities.