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1.
Ann Oncol ; 23(5): 1178-1184, 2012 May.
Article in English | MEDLINE | ID: mdl-21965471

ABSTRACT

BACKGROUND: We evaluated the prognostic importance of DNA ploidy in stage I and II endometrioid adenocarcinoma (EAC) of the endometrium with a focus on DNA index. PATIENTS AND METHODS: High-resolution DNA ploidy analysis was carried out in tumor material from 937 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage I and II EAC of the endometrium. RESULTS: Patients with diploid (N = 728), aneuploid tumor with DNA index ≤ 1.20 (N = 118), aneuploid tumors with DNA index >1.20 (N = 39) and tetraploid tumor (N = 52) had 5-year recurrence rates 8%, 14%, 20% and 12%, respectively. Patients with aneuploid tumor with DNA index >1.20 had a poorer 5-year progression-free survival (67%) and overall survival (72%) compared with the patients with aneuploid tumor with DNA index ≤ 1.20 (81% and 89%, respectively). Aneuploid tumors with DNA index ≤ 1.20 relapsed mainly in the vagina and pelvis, whereas aneuploid tumors with DNA index >1.20 relapsed predominantly outside pelvis. CONCLUSIONS: The recurrence risk for the patients with aneuploid tumor is higher than the patients with diploid tumor in EAC of the endometrium. Based on DNA index with cut-off 1.20, aneuploid tumors can be separated into two subgroups with different recurrence pattern and survival.


Subject(s)
Carcinoma, Endometrioid/diagnosis , DNA, Neoplasm/genetics , Endometrial Neoplasms/diagnosis , Mitotic Index , Ploidies , Adult , Aged , Aged, 80 and over , Aneuploidy , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , DNA, Neoplasm/analysis , Endometrial Neoplasms/genetics , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Endometrium/metabolism , Endometrium/pathology , Female , Humans , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Survival Analysis
2.
Eur J Gynaecol Oncol ; 30(5): 471-82, 2009.
Article in English | MEDLINE | ID: mdl-19899396

ABSTRACT

The 5-year survival for women with Stage-I borderline tumours (BOT) is favourable, about 95-97%, but the 10-year survival is only between 70 and 95%, caused by late recurrence. The 5-year survival for Stage II-III patients is 65-87%. Standard primary surgery includes bilateral SOEB, omentectomy, peritoneal washing and multiple biopsies. Second cytoreductive surgery is recommended for patients with recurrent disease. Adjuvant postoperative therapy is not indicated in Stage-I diploid tumors. Occasional responses to chemotherapy have been reported in advanced BOTs but no study has shown improved survival. Recently a new theory has been developed describing a subset of S-ovarian cyst adenomas that evolve through S-BOT to low-grade carcinoma. A more correct staging procedure, classification of true serous implants and agreement on the contribution to stage of the presence of gelatinous ascites in mucinous tumours may in the future change the distribution of stage and survival data by stage for women with BOT. Independent prognostic factors in patients with epithelial ovarian BOT without residual tumour after primary surgery are DNA-ploidy, international FIGO-stage, histologic type and patient age. Studies on other molecular markers have not yet uncovered a reliable prediction of biologic behaviour, however, there is hope that future studies of genetics and molecular biology of these tumours will lead to useful laboratory tests. Future questions to be addressed in this review include the following: Have patients with borderline tumours in general been over-treated and how should these patients be treated? How to define the high-risk patients? In which group of patients is fertility-sparing surgery advisable and, do patients with borderline tumours benefit from adjuvant treatment?


Subject(s)
Cystadenoma, Mucinous/pathology , Cystadenoma, Mucinous/surgery , Cystadenoma, Serous/pathology , Cystadenoma, Serous/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Cystadenoma, Mucinous/physiopathology , Cystadenoma, Serous/physiopathology , Disease Progression , Female , Humans , Neoplasm Staging , Ovarian Neoplasms/physiopathology , Ovariectomy , Prognosis
3.
Ann Oncol ; 20(6): 1037-41, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19201782

ABSTRACT

BACKGROUND: The diagnosis of uterine sarcoma is associated with poor outcome for the patient and there is a need for reliable prognostic markers. Most previous studies on the prognostic value of DNA ploidy include few uterine sarcomas and report conflicting results. MATERIALS AND METHODS: We examined the prognostic value of DNA ploidy and its association with clinicopathological parameters and crude survival in a total population of 354 sarcoma. RESULTS: In univariate analyses, we observed significantly better crude survival for endometrial stromal sarcomas (ESS) and adenosarcoma (AS) patients with diploid as compared with nondiploid tumors, but not for patients with leiomyosarcomas (LMS). In Cox multivariate analyses, DNA ploidy was the only significant predictor of survival for patients with AS. In LMS, mitotic index (MI), tumor size, tumor extent and tumor margins, whereas for ESS, MI, tumor extent and tumor necrosis obtained independent significance of survival. DNA ploidy was a significant predictor of survival for LMS patients in Cox regression analyses when excluding MI. CONCLUSION: DNA ploidy might be useful as a prognostic marker in patients with LMS and AS.


Subject(s)
Ploidies , Sarcoma/genetics , Uterine Neoplasms/genetics , Female , Genomic Instability , Humans , Middle Aged , Prognosis , Sarcoma/pathology , Survival Analysis , Uterine Neoplasms/pathology
4.
Int J Med Robot ; 3(3): 224-8, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17924449

ABSTRACT

BACKGROUND: We evaluated the feasibility and efficacy of robotic-assisted laparoscopic radical hysterectomy and bilateral pelvic lymph node dissection for early cervical carcinoma, comparing the results with those from conventional total laparoscopic radical hysterectomy. METHODS: Type II and III radical hysterectomies were performed in 15 patients with early-stage cervical carcinoma as a pilot case-control study at a comprehensive cancer center-university teaching hospital setting. The adequacy of the operations was determined and documented in DVD/video. RESULTS: All operations were performed according to a well-established study protocol. No conversions or technical incidents were observed in the robotic group. Median operation time was 241 and 300 min in the robotic and conventional laparoscopic groups, respectively (p = 0.165). The histopathological results concerning the number of lymph nodes, the parametrial tissue and vaginal cuff size were similar in both groups. Less bleeding and a shorter hospital stay were observed in the robotic-assisted group (p = 0.038 and p = 0.004, respectively). CONCLUSIONS: Although the benefits of this technique have not yet been established in a prospective randomized manner, we showed the technical feasibility of robotic-assisted laparoscopic radical hysterectomy in early-stage cervical carcinoma cases and better results than with traditional total laparoscopic radical hysterectomy.


Subject(s)
Hysterectomy/methods , Laparoscopy/methods , Robotics/methods , Surgery, Computer-Assisted/methods , Uterine Cervical Neoplasms/surgery , Feasibility Studies , Female , Forecasting , Humans , Neoplasm Staging , Treatment Outcome , Uterine Cervical Neoplasms/pathology
5.
Eur J Gynaecol Oncol ; 27(5): 513-8, 2006.
Article in English | MEDLINE | ID: mdl-17139990

ABSTRACT

OBJECTIVE: The objective of this study is to describe a new technique of laparoscopic radical hysterectomy without vaginal cuff closure. METHODS: Three patients underwent laparoscopic radical hysterectomy, bilateral salpingo-oophorectomy and bilateral pelvic lymph node dissection using an Argon Beam Coagulator. Four trocars were used: umbilical port for the camera, two ports for the operating surgeon and a fourth port for use by the surgical assistant. RESULTS: All patients were clinically staged IB1. Ages were 53, 64 and 58 and BMI was 19.5, 25.2 and 21.4, respectively. Duration of surgery was 375, 325 and 335 minutes, respectively, from first trocar insertion to last closing stitch. Estimated blood loss was 300, 100 and 400 ml and removed pelvic lymph nodes 18, 15 and 26, respectively. The patients tolerated the surgical technique and recovered satisfactorily. CONCLUSION: These are the first three cases of early-stage cervical carcinoma patients who have been treated with entirely laparoscopic abdominal radical hysterectomy (LARH) and bilateral pelvic lymphadenectomy (BPL) without vaginal cuff closure. To our knowledge, this has not been previously described in the literature. It is feasible and was well tolerated in this small series of patients.


Subject(s)
Adenocarcinoma/surgery , Carcinoma, Squamous Cell/surgery , Hysterectomy/methods , Laparoscopy/methods , Uterine Cervical Neoplasms/surgery , Female , Humans , Lymph Node Excision , Middle Aged , Neoplasm Staging
6.
Eur J Gynaecol Oncol ; 27(5): 531-3, 2006.
Article in English | MEDLINE | ID: mdl-17139995

ABSTRACT

OBJECTIVE: The aim of this study was to describe the first robotic-assisted radical hysterectomy (Piver type III) and bilateral pelvic lymph node dissection for a patient with Stage Ib1 cervical carcinoma. CASE: A 43-year-old woman G1, P1, previously operated on due to endometriosis with removal of the left ovary and fallopian tube, came under our care. In addition, hysteroscopic myomectomy had been done two years before. Otherwise the patient was healthy. Preoperative conization histology revealed 6 mm of stromal infiltration. The patient was offered the da Vinci robotic Wertheim operation for the first time which was well accepted and she was discharged uneventfully on the 4th day postoperatively. Four months later at a routine check-up we found asymptomatic bilateral lymphocysts but otherwise normal status. CONCLUSION: It is fully possible to perform Piver type III laparoscopic radical hysterectomy using the da Vinci robotic system and it seems that radical dissection is much more precise than the conventional laparoscopic radical hysterectomy.


Subject(s)
Carcinoma in Situ/surgery , Carcinoma, Squamous Cell/surgery , Hysterectomy/methods , Lymph Node Excision/methods , Robotics , Uterine Cervical Neoplasms/surgery , Adult , Female , Humans , Laparoscopy/methods
7.
J Pathol ; 210(4): 441-9, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17029216

ABSTRACT

Testicular germ cell tumours (TGCTs) are classified into two main histological subgroups: seminomas and non-seminomas. The latter comprise several subtypes: embryonal carcinomas, yolk sac tumours, choriocarcinomas, and teratomas. These embryonal and extra-embryonal-like differentiation lineages represent a caricature of early normal development, and inactivation of gene expression through promoter hypermethylation may therefore be of particular importance in germ cell tumourigenesis. The promoter methylation status of ten candidate genes-CDH13, DLX6, EMX2, HOXA9, HOXB5, MSX1, MSX2, RASSF1A, RUNX3, and SCGB3A1 (alias HIN-1)-was assessed by methylation-specific PCR in seven intratubular germ cell neoplasias and 55 primary TGCTs. Furthermore, by a discovery-based global approach, comparing cDNA microarray expression profiles of two germ cell tumour cell lines before and after treatment with the demethylating agent 5-aza-2'-deoxycytidine, a gene list of potentially epigenetic targets was identified, from which CGGBP1, CGRRF1, SMARCC2, SORBS1, and XPA were analysed further. Overall, the non-seminomas were significantly more often methylated than were seminomas (p < 0.001). The three most frequently methylated genes among this subtype were SCGB3A1 (54%), RASSF1A (29%), and HOXA9 (26%). CDH13 and HOXB5 were methylated at low frequencies (10-15%), and EMX2, MSX1, RUNX3, SORBS1, and XPA only rarely (<10%). In conclusion, this study has identified several novel epigenetically deregulated target genes in TGCT development, including homeobox genes and SCGB3A1, suggesting that epigenetic inactivation of key genes in normal development also has an important role in TGCTs.


Subject(s)
Cytokines/genetics , Genes, Homeobox/genetics , Neoplasms, Germ Cell and Embryonal/genetics , Testicular Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Carcinoma, Embryonal/genetics , Cell Line, Tumor , DNA, Neoplasm/genetics , Endodermal Sinus Tumor/genetics , Epigenesis, Genetic/genetics , Gene Expression Regulation, Neoplastic/genetics , Homeodomain Proteins/genetics , Humans , Male , Methylation , Neoplasm Proteins/genetics , Oligonucleotide Array Sequence Analysis/methods , Polymerase Chain Reaction/methods , Seminoma/genetics , Teratoma/genetics
8.
Int J Gynecol Cancer ; 14(6): 1118-21, 2004.
Article in English | MEDLINE | ID: mdl-15571618

ABSTRACT

Uterine adenosarcoma (UAS) is microscopically characterized by a biphasic growth pattern. By definition, the epithelial component is benign, whereas the stromal component typically has the appearance of a low-grade sarcoma, usually an endometrial stromal sarcoma. CD10 acts by reducing cellular response to peptide hormones and is currently regarded as a specific marker for endometrial stromal tumors. In this international multicenter study, we further explored CD10 immunoreactivity in 30 UASs. We encountered CD10 positivity of the sarcomatous component in 18/20 (90%) of UASs, in five of eight (63%) of UASs with sarcomatous overgrowth as well as in both cases of recurrent UAS. The epithelial component stained negative in all cases. These findings suggest that CD10 can be used to differentiate UAS from cellular leiomyoma, or in case endometrial stromal cells exhibit muscle differentiation. Furthermore, CD10 positivity in recurrent UAS might guide the pathologist toward an endometrial stromal origin.


Subject(s)
Adenosarcoma/metabolism , Biomarkers, Tumor/metabolism , Neprilysin/metabolism , Uterine Neoplasms/metabolism , Adenosarcoma/epidemiology , Adenosarcoma/etiology , Adenosarcoma/pathology , Adult , Aged , Aged, 80 and over , Europe/epidemiology , Female , Humans , Immunohistochemistry , Leiomyoma/epidemiology , Leiomyoma/etiology , Leiomyoma/metabolism , Leiomyoma/pathology , Middle Aged , Predictive Value of Tests , Uterine Neoplasms/epidemiology , Uterine Neoplasms/etiology , Uterine Neoplasms/pathology
9.
Eur J Cancer ; 40(7): 1058-65, 2004 May.
Article in English | MEDLINE | ID: mdl-15093583

ABSTRACT

This case-control study based in Nordic serum banks evaluated the joint effects of infections with genital human papillomavirus (HPV) types, and Chlamydia trachomatis in the aetiology of cervical squamous cell carcinoma. Through a linkage with the cancer registries, 144 cases were identified and 420 controls matched to them. Exposure to past infections was defined by the presence of specific IgG antibodies. The odds ratio (OR) for the second-order interaction of HPV16, HPV6/11 and C. trachomatis was small (1.0) compared to the expected multiplicative OR, 57, and the additive OR, 11. The interactions were not materially different among HPV16 DNA-positive squamous cell carcinomas. When HPV16 was replaced with HPV18/33 in the analysis of second-order interactions with HPV6/11 and C. trachomatis, there was no evidence of interaction, the joint effect being close to the expected additive OR. Possible explanations for the observed antagonism include misclassification, selection bias or a true biological phenomenon with HPV6/11 and C. trachomatis exposures antagonizing the carcinogenic effects of HPV16.


Subject(s)
Carcinoma, Squamous Cell/virology , Chlamydia Infections/complications , Papillomavirus Infections/complications , Uterine Cervical Neoplasms/microbiology , Adult , Carcinoma, Squamous Cell/epidemiology , Case-Control Studies , Cervix Uteri/microbiology , Cervix Uteri/virology , Chlamydia Infections/epidemiology , DNA, Viral/isolation & purification , Female , Finland/epidemiology , Humans , Middle Aged , Multivariate Analysis , Norway/epidemiology , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Regression Analysis , Risk Factors , Sweden/epidemiology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/virology
10.
Br J Cancer ; 90(3): 678-85, 2004 Feb 09.
Article in English | MEDLINE | ID: mdl-14760384

ABSTRACT

We conducted the present study to evaluate the frequency and prognostic importance on long-term survival of TP53 mutations and TP53 protein accumulation in a cohort of 178 patients with early-stage ovarian carcinomas. TP53 mutations scored as aberrant temporal temperature gradient gel electrophoresis pattern from all exons were observed in 39.9% of the tumours. Full screening of exons 5-8, followed by sequencing, was successful in 135 cases, and 48 mutations altering the protein were detected in 39 cases (28.9%). TP53 mutations were slightly less common in the Federation of Gynecologists and Obstetricians stage IA than in IB/IC (P=0.05). No significant correlations with histological type, grade of differentiation, DNA ploidy status or age at diagnosis were found. TP53 protein accumulation analysed by immunohistochemistry was found in 32.6% of all tumours, and was a poor predictor of TP53 mutations with 56.4% sensitivity, 77.1% specificity, 50% positive predictive value and 81.3% negative predictive value. Neither TP53 mutations nor TP53 protein accumulation influenced the prognosis significantly in this group of patients.


Subject(s)
Genes, p53/genetics , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Tumor Suppressor Protein p53/genetics , Aged , Cohort Studies , DNA Mutational Analysis , DNA, Neoplasm , Electrophoresis, Gel, Two-Dimensional , Exons , Female , Humans , Immunohistochemistry , Middle Aged , Neoplasm Staging , Ploidies , Predictive Value of Tests , Prognosis , Survival Analysis , Tumor Suppressor Protein p53/analysis
11.
Ann Oncol ; 14(10): 1494-500, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14504048

ABSTRACT

BACKGROUND: The objective was to evaluate the value of DNA ploidy using high-resolution image cytometry in predicting long-term survival of patients with early ovarian cancer. PATIENTS AND METHODS: A retrospective analysis of 284 cases with FIGO stage I ovarian carcinoma treated during the period 1982-1989 was performed. Clinical follow-up information was available for all patients. RESULTS: Patients with diploid and tetraploid tumors had a 10-year relapse-free survival of 95% and 89%, respectively, compared with 70% and 29% for polyploid and aneuploid tumors, respectively. DNA ploidy analysis was the strongest predictor of survival in multivariate analysis (diploid/tetraploid versus polyploid/aneuploid; relative hazard 9.0) followed by histological grade, including clear cell tumors in the group of poorly differentiated tumors (grade 1-2 versus grade 3 or clear cell; relative hazard 2.7), and FIGO stage (Ib/Ic versus Ia; relative hazard 2.0). In a stratified Kaplan-Meier analysis, patients with grade 1-2, diploid or tetraploid tumors had a 10-year relapse-free survival of 95%, forming a low-risk group. Patients with grade 3 or clear cell, diploid or tetraploid tumors had 10-year relapse-free survival of 86%, forming an intermediate-risk group, while all patients with aneuploid/polyploid tumors formed a high-risk group, with 10-year relapse-free survival of 34%. CONCLUSIONS: This study points to the importance of including DNA ploidy analysis by image cytometry when selecting patients with early ovarian cancer for adjuvant treatment after surgery.


Subject(s)
Genomic Instability , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Adult , Aged , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Image Cytometry , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/surgery , Patient Selection , Ploidies , Predictive Value of Tests , Prognosis , Radiotherapy, Adjuvant , Retrospective Studies , Risk Factors
12.
Gynecol Oncol ; 87(1): 71-6, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12468345

ABSTRACT

OBJECTIVES: The aim of this study was to give an overview of the Norwegian population of gestational trophoblastic tumors (GTT), diagnosed during 1968-1997 and treated with chemotherapy at the Norwegian Radium Hospital (NRH), with regard to patient characteristics, treatment, and prognosis. METHODS: The cases were grouped according to a modified version of the WHO scoring system. Staging was performed retrospectively according to the systems adopted by FIGO. Survival estimates were calculated by the method described by Kaplan and Meier. Cox regression models were used to find the best classification system with regard to prognosis (disease-free survival). RESULTS: A total of 141 cases, 106 invasive moles (IM) and 35 choriocarcinomas (CC), were diagnosed in Norway and treated with chemotherapy at the NRH in the period 1968-1997. Altogether, 56% of the patients were assigned to the low-risk category, 20% to the medium-risk category, and 15% to the high-risk category. Most cases were classified into the clinical stages I (69%) and III (23%). The overall 5-year survival rate was 96%. A more favorable prognosis was seen in patients diagnosed in the 1980s and 1990s compared with those diagnosed in the 1970s (P = 0.04). Five patients had progressive disease and died from the disease. Nine patients relapsed. The prognosis (disease-free survival) was more favorable for IM compared with CC (P < 0.01). The FIGO classification system seemed to be a better predictor of disease-free survival than the WHO scoring system. CONCLUSIONS: This study showed that the prognosis of patients with GTT improved in the 1980s and 1990s in Norway, and that the FIGO system might be the best predictor of disease-free survival.


Subject(s)
Trophoblastic Neoplasms/drug therapy , Trophoblastic Neoplasms/pathology , Uterine Neoplasms/drug therapy , Uterine Neoplasms/pathology , Adolescent , Adult , Female , Follow-Up Studies , Humans , Middle Aged , Norway/epidemiology , Pregnancy , Prognosis , Trophoblastic Neoplasms/epidemiology , Uterine Neoplasms/epidemiology
13.
Br J Cancer ; 87(2): 175-80, 2002 Jul 15.
Article in English | MEDLINE | ID: mdl-12107839

ABSTRACT

Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2-8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P<0.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P<0.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA.


Subject(s)
Antibodies, Viral/blood , Carcinoma, Squamous Cell/epidemiology , DNA, Viral/isolation & purification , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Precancerous Conditions/epidemiology , Tumor Virus Infections/epidemiology , Uterine Cervical Neoplasms/epidemiology , Adult , Carcinoma, Squamous Cell/virology , Case-Control Studies , DNA Probes, HPV , DNA, Viral/blood , Female , Finland/epidemiology , Follow-Up Studies , Humans , Mass Screening , Middle Aged , Norway/epidemiology , Papillomaviridae/classification , Papillomaviridae/genetics , Papillomaviridae/immunology , Papillomavirus Infections/diagnosis , Polymerase Chain Reaction , Precancerous Conditions/diagnosis , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Prospective Studies , Risk , Seroepidemiologic Studies , Tumor Virus Infections/diagnosis , Uterine Cervical Neoplasms/virology
14.
Cancer ; 92(9): 2471-83, 2001 Nov 01.
Article in English | MEDLINE | ID: mdl-11745305

ABSTRACT

BACKGROUND: The incidence of adenocarcinoma of the uterine cervix is increasing. For better prognostic information, the authors studied all nonsquamous cell carcinomas (non-SCCs) in the Norwegian population over a total of 15 years. METHODS: All non-SCCs from three 5-year periods (1966-1970, 1976-1980, and 1986-1990) were reviewed and classified according to the World Health Organization classification system, and histopathologic and clinical parameters were registered. Tissue blocks were available from all patients. RESULTS: Of 505 patients, 417 had tumors classified as adenocarcinoma, and 88 had tumors classified as other non-SCC. The mean ages were 53 years and 52 years for patients with adenocarcinoma and non-SCC, respectively. Sixty-two percent of the staged patients had clinical Stage I disease according to the classification system of the International Federation of Gynecology and Obstetrics (FIGO). In univariate analyses, histology, architectural and nuclear grade, extension to the vagina or corpus uteri, tumor length (> 20 mm) or tumor volume (> 3000 mm(3)), infiltration depth (in thirds of the cervical wall), thickness of the remaining wall (< 3 mm), vascular invasion, lymph node metastases, treatment, and patient age were significant variables in patients with FIGO Stage I disease. Variables with no significance in patients with Stage I disease were number of mitoses, state of resection margins, infiltration to ectocervix, tumor thickness, lymphoid reaction, earlier or concomitant cervical intraepithelial neoplasia, stump carcinoma, DNA ploidy or DNA index, or time period. Multivariate analyses of patients with FIGO Stage I disease identified small cell carcinoma, corpus infiltration, vascular invasion, and positive lymph nodes as independent prognostic factors. CONCLUSIONS: Small cell carcinoma was the only histologic subgroup of independent importance for prognosis in patients with non-SCC of the uterine cervix. No significant difference between major subtypes of adenocarcinoma favored a simplified classification. Extension to the corpus in patients with early-stage disease was of independent significance and should be acknowledged in planning treatment.


Subject(s)
Adenocarcinoma/pathology , Carcinoma, Small Cell/pathology , Neoplasm Staging , Uterine Cervical Neoplasms/pathology , Adult , Age Factors , Aged , DNA, Neoplasm/genetics , Female , Humans , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Ploidies , Prognosis , Risk Factors , Survival Analysis
15.
Tidsskr Nor Laegeforen ; 121(23): 2723-7, 2001 Sep 30.
Article in Norwegian | MEDLINE | ID: mdl-11699381

ABSTRACT

BACKGROUND: Less than radical vulvectomy for primary vulvar cancer has been controversial. Less mutilating surgery without sacrificing benefits in prognosis is warranted. MATERIAL AND METHODS: Based on relevant literature and our own experience, we give a review of surgery and sentinel node examination in early vulvar cancer. RESULTS: Regional lymph node metastasis rarely occurs when tumour thickness is less than 1 mm. Smaller lesions (< 2 cm in diameter) should therefore be treated by wide excision only and without lymph node dissection. Other T1 lesions with deeper invasion should be radically excised with at least 2 cm margins and extend deep to the inferior fascia of the urogenital diaphragm. Complete inguinal-femoral lymphadenectomy should be performed in patients without groin metastases to avoid a small, but definite risk of recurrence, although the incidence of lymph node metastases for all clinical stage I patients is less than 10%. Lymphatic mapping with 99mTechnetium and patent blue technique is a potentially valuable intraoperative tool for assuring removal of the sentinel node most likely to have metastasis, defining the extent of the superficial inguinal lymphadenectomy and identifying uncommon anatomic variations. INTERPRETATION: Until reliable data on the benefits of selective lymphadenectomy using intraoperative lymphoscintigraphy are available, the procedure should only be performed in an approved research setting.


Subject(s)
Sentinel Lymph Node Biopsy , Vulvar Neoplasms/surgery , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Medical Illustration , Neoplasm Staging , Practice Guidelines as Topic , Prognosis , Vulvar Neoplasms/mortality , Vulvar Neoplasms/pathology
16.
Best Pract Res Clin Obstet Gynaecol ; 15(3): 433-46, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11476564

ABSTRACT

Clear-cell carcinoma (CCC) and serous papillary carcinoma of the endometrium (UPSC) are rare subtypes of endometrial carcinoma (10%). The histological diagnosis can be made on the dilation and curettage specimens in both types in a very high percentage of the cases. This is important in the planning of treatment. CCC and UPSC are associated with about 50% of all relapses occurring in endometrial carcinoma, and the 5-year survival rate is, on average, 42% and 27% respectively. Surgico-pathological stage, age, and vessel invasion are independent prognostic factors for both groups. The recurrence rate is extremely high, and the most frequent extra-pelvic sites of relapse are the upper abdomen, lungs and liver. Stage Ia patients treated with complete surgical staging alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. The treatment of patients with CCC and UPSC stage Ib, Ic, II and III should include radical debulking surgery and some form of adjuvant therapy, but it is not clear which type is most effective. Adjuvant pelvic radiotherapy plus intracavitary radiotherapy is usually given in early-stage disease and pelvic radio therapy/or whole abdomen irradiation plus adjuvant systemic chemotherapy (PAC) in advanced disease. However, we are urgently waiting for a large prospective randomized study to compare both modalities. Paclitaxel, alone or in combination, is currently being tested in phase II studies.


Subject(s)
Adenocarcinoma, Clear Cell/therapy , Cystadenocarcinoma, Papillary/therapy , Endometrial Neoplasms/therapy , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Clear Cell/secondary , Age Factors , Aneuploidy , Combined Modality Therapy , Cystadenocarcinoma, Papillary/pathology , Cystadenocarcinoma, Papillary/secondary , Dilatation and Curettage , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Female , Genes, p53 , Humans , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Neoplasm Invasiveness/genetics , Neoplasm Staging , Prognosis , Transcriptional Activation , Treatment Outcome
17.
Anal Cell Pathol ; 23(2): 45-9, 2001.
Article in English | MEDLINE | ID: mdl-11904459

ABSTRACT

Fibroblast growth factor receptor 3 (FGFR3) seems to play an inhibitory role in bone development, as activating mutations in the gene underlie disorders such as achondroplasia and thanatophoric dysplasia. Findings from multiple myeloma (MM) indicate that FGFR3 also can act as an oncogene, and mutation of codon 249 in the fibroblast growth factor receptor 3 (FGFR3) gene was recently detected in 3/12 primary cervical carcinomas. We have analysed 91 cervical carcinomas for this specific S249C mutation using amplification created restriction site methodology (ACRS), and detected no mutations. Immunohistochemistry was performed on 73 of the tumours. Reduced protein staining was seen in 43 (58.8%) samples. Six of the tumours (8.2%) revealed increased protein staining compared with normal cervical tissue. These patients had a better prognosis than those with reduced or normal levels, although not statistically significant. This report weakens the hypothesis of FGFR3 as an oncogene of importance in cervical carcinomas.


Subject(s)
Point Mutation , Protein-Tyrosine Kinases , Receptors, Fibroblast Growth Factor/analysis , Receptors, Fibroblast Growth Factor/genetics , Uterine Cervical Neoplasms/chemistry , Uterine Cervical Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Middle Aged , Prognosis , Receptor, Fibroblast Growth Factor, Type 3 , Uterine Cervical Neoplasms/genetics
18.
Tidsskr Nor Laegeforen ; 120(23): 2764-70, 2000 Sep 30.
Article in Norwegian | MEDLINE | ID: mdl-11107921

ABSTRACT

Only within the last decade we have begun to fully appreciate the natural history and biologic behaviour of borderline tumours in the ovaries. In contradiction to invasive epithelial tumours, most borderline tumours are confined to the ovary(ies) (stage I). Because the prognosis of stage I serous borderline tumours is excellent, with five-year survival rates of almost 100%, some experts are advocating that this subset should be classified as benign. Although the standard treatment for older patients is abdominal hysterectomy and bilateral salpingo-oophorectomy, many young patients who have not completed childbearing can be safely treated with unilateral salpingo-oophorectomy coupled with comprehensive surgical staging, thereby preserving their fertility potential. Another major controversy associated with borderline tumours is the clinical management of patients with advanced-stage disease or peritoneal implants. Many experts strongly believe that surgery is the only effective treatment for borderline tumours. Others routinely employ postoperative chemotherapy for at least some subset of patients with peritoneal implants. Several investigators have focused on DNA ploidy as a predictor of recurrence and survival, but their findings are conflicting.


Subject(s)
Ovarian Neoplasms/diagnosis , Controlled Clinical Trials as Topic , Female , Genes, Tumor Suppressor , Humans , Mutation , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Ploidies , Prognosis , Randomized Controlled Trials as Topic , Survival Rate
19.
Cancer ; 89(10): 2076-84, 2000 Nov 15.
Article in English | MEDLINE | ID: mdl-11066048

ABSTRACT

BACKGROUND: The objective of the current study was to increase insight into the biology of fallopian tube carcinoma through an analysis of possible clinical and pathologic determinants of prognosis and to formulate recommendations with regard to a more optimal therapeutic approach for patients with this rare disease. METHODS: A study was performed of the pathology specimens and clinical case records from 151 patients with fallopian tube carcinoma who were treated consecutively. Both univariate and multivariate analyses of possible prognostic factors were performed for the whole group and for the subgroup of 41 patients with Stage I disease. The possible significance of serum CA-125 levels as a tumor marker and a marker of response to platinum-containing chemotherapy was evaluated. RESULTS: In multivariate analysis, disease stage, the presence of residual tumor, and a hydrosalpinx-like appearance of the fallopian tube were of independent prognostic significance for the whole cohort. For patients with Stage I disease, the depth of infiltration in the tubal wall and intraoperative tumor rupture were of independent prognostic significance. The marked tendency of this disease for extraperitoneal spread, even in apparently early stages, was confirmed. In 37 evaluable, platinum-naïve patients, an overall response rate of 70% was obtained with platinum-based chemotherapy, with a median response duration of 12.5 months. In view of its low efficacy and high rate of serious complications, the use of postoperative radiotherapy in the treatment of patients with fallopian tube carcinoma is no longer recommended. Serum CA-125 level measurements in fallopian tube carcinoma patients have the same significance as tumor and surrogate markers of response as in ovarian carcinoma patients. CONCLUSIONS: Prognostic factors in patients with early stage (Stages 0 and I) fallopian tube carcinoma seem to differ from those in patients with early stage ovarian carcinoma. For patients with more advanced stage disease, due to the striking similarities in prognostic and clinical characteristics between the two diseases, the authors recommend that the treatment and follow-up strategies for patients with ovarian carcinoma be adopted in the management of patients with fallopian tube carcinoma.


Subject(s)
Adenocarcinoma/diagnosis , Fallopian Tube Neoplasms/diagnosis , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Fallopian Tube Neoplasms/mortality , Fallopian Tube Neoplasms/pathology , Female , Humans , Middle Aged , Multivariate Analysis , Neoplasm Staging , Norway/epidemiology , Postoperative Care , Prognosis , Recurrence , Survival Analysis
20.
Cancer ; 89(6): 1291-9, 2000 Sep 15.
Article in English | MEDLINE | ID: mdl-11002225

ABSTRACT

BACKGROUND: The effect of histopathologic review and subclassification on incidence rates for nonsquamous cell carcinoma (non-SCC) of the uterine cervix in the Norwegian population was evaluated. METHODS: All non-SCC from three 5-year periods (1966-70, 1976-80, and 1986-90) were reviewed, classified, and graded. RESULTS: Incidence rates were 1.2, 1.2, and 1.7 per 100,000 for adenocarcinoma and 0.1, 0.3, and 0.5 per 100,000 for other carcinomas in the three periods. Adenocarcinomas increased in all age groups, most markedly in women younger than 35 years. Incidence rates for both major subgroups of endocervical (EC) and endometrioid (EM) carcinomas increased for women younger than 55 years. After 1976-80, the incidence rate for EC, but not for EM, decreased in women older than 55 years. Endometrioid carcinoma became the dominant histologic subtype in 1986-90. Shifts toward lower clinical stages and younger age were found for EC, EM, and carcinoma not otherwise specified (NOS). Patients with NOS, clear cell, serous, or glassy cell/undifferentiated carcinoma were older, and their disease was diagnosed at higher stages. Distribution of International Federation of Gynecology and Obstetrics (FIGO) stages was: Stage I: 62%; Stage II: 21%; Stage III: 12%; and Stage IV: 5%. Distribution of histologic subgroups was: EC:, 24%; EM: 21%; NOS: 16%; clear cell: 7%; adenosquamous: 7%; small cell: 6%; serous: 4%; undifferentiated: 3%; and villoglandular carcinoma: 2%. Other subgroups were seen only sporadically. CONCLUSIONS: Incidence rates of non-SCC of the uterine cervix are increasing in Norway. Improvements in diagnostic procedures may explain shifts toward lower stage and age of patients but not the observed differences between histologic subgroups.


Subject(s)
Adenocarcinoma/epidemiology , Adenocarcinoma/pathology , Carcinoma, Endometrioid/epidemiology , Carcinoma, Endometrioid/pathology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/classification , Adult , Age Factors , Carcinoma, Endometrioid/classification , Female , Humans , Incidence , Middle Aged , Neoplasm Staging , Norway/epidemiology , Uterine Cervical Neoplasms/classification
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