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Prognostic Factors in Early Stage Cervical Carcinomas Treated with Wertheim-Meigs Surgery
Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cervical cancer is the second most common malignancy and a leading cause of morbidity and mortality among women worldwide. In Sweden, cervical cancer constitutes 2.4% of all newly diagnosed cancers and is the fifteenth cause of death.

An improved estimation of the prognosis in early stages of cervical carcinomas is desirable. The most important of the established prognostic factors are tumor size, radical excision margins, and lymph node status. The objectives of this study were to assess the value of oncogene and tumor suppressor gene products, angiogenesis, proliferation markers and histopathological malignancy grading systems as predictors of pelvic lymph node metastases (LNM), tumor recurrences and death due to the disease in early stage (FIGO I-II).

In a complete geographic series of cervical carcinomas treated by Wertheim-Meigs surgery, a number of clinical, biological, and histopathological prognostic factors were evaluated and long-term survival data were presented. In all, 367 woman with FIGO stage I-II cervical tumors were included.

Significant prognostic factors for disease-free survival were lymph node status, radical surgical margins, and tumor size. In a multivariate Cox analysis, it was shown that lymph node status was the single most important prognostic factor (P < 0.0000001). Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage. There was also a significant (P = 0.002) association between the vascular space invasion of tumor cells and the presence of lymph node metastases.

The complete malignancy grading system (MGS), partial index (PI), and invasive front grading (IFG) scores were highly significantly (P = 0.0001, P = 0.0001, P = 0.002) associated with the presence of pelvic LNM and with the disease-free survival rate. No pelvic lymph node metastases were encountered in tumors with MGS scores below 16. The predictive value (the specificity) for no pelvic lymph node metastases was 97%. The complete IFG score and the individual scores of the two variables, pattern of invasion and host response, were all significantly (P = 0 .002, P = 0.007, P = 0.0001) associated with pelvic LNM. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting LNM.

The activity of the proliferation marker MIB-1 was lower in pelvic lymph node metastases than in the primary tumors. The expression ofMIB-1 in lymph nodes was a prognostic factor for disease-free survival in both univariate and multivariate analyses.

In our series, it was concluded that microvessel density (CD31) and expressions of p53, bcl-2, p21 (WAF1), DNA ploidy, and S-phase fraction (FCM) did not add any further predictive or prognostic information.

In conclusion, this study has confirmed that histopathological malignancy grading (MGS), the partial index (PI), and invasive front grading (IFG) in the original or modified versions can predict low and high-risk groups of tumors and therefore be of value in planning the treatment of early stage squamous cell carcinomas of the uterine cervix. The expression of the proliferative marker MIB-1 in primary tumors and in LNM seems to be a factor that should be studied further in an attempt to identify different prognostic groups of tumors requiring more individualized postoperative treatment planning.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2002. , 63 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 732
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25648Local ID: 10024ISBN: 91-7373-177-3 (print)OAI: oai:DiVA.org:liu-25648DiVA: diva2:246196
Public defence
2002-05-24, Wilandersalen, Universitetssjukhuset, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-13Bibliographically approved
List of papers
1. Treatment of cervical carcinoma by Wertheim-Meigs surgery: Long-term follow-up results in a well-defined Swedish region
Open this publication in new window or tab >>Treatment of cervical carcinoma by Wertheim-Meigs surgery: Long-term follow-up results in a well-defined Swedish region
Show others...
1995 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 6, no 4, 817-823 p.Article in journal (Refereed) Published
Abstract [en]

In a retrospective analysis of a complete geographic series of cervical carcinomas treated by Wertheim-Meigs radical surgery, a number of important prognostic factors were evaluated and long-term survival data are presented. In all, 367 women with FIGO stage I-II tumors were included. The main histopathologic types were squamous cell carcinoma in 84% and adenocarcinoma in 12%. The mean age of the patients was 42.5 (range 19-68) years. In 125 women (34%), adjuvant radiotherapy was administered pre- or postoperatively. The median period of follow-up was 12 (range 2-27) years. In 88% of the specimens surgery (93% in stage I and 66% in stage II) was classified as radical with regard to the excision margins. This was an important and highly significant prognostic factor. If the margins were wide and free of tumor, the 10-year survival rate was 93%, but if margins were infiltrated by the tumor, the survival rate was 14%. Pelvic lymph node involvement was recorded in 52 cases (14%). The frequency of lymph node spread was associated with tumor stage (IA O%, IB 14%, IIA 32%). The probability of survival of the complete series was 93% at 5 years and 84% at 10 years. In cases of lymph node involvement, the 10-year survival rate was 57%. The preoperative tumor stage had a highly significant influence on long-term tumor-specific survival. Tumor grade was also a significant prognostic factor, but not the histologic type (squamous, adenosquamous, or adenocarcinoma). Age and parity were also insignificant prognostic factors. The tumor recurred in 59 cases (16%). The mean time to relapse was 28 months. The 10-year survival was 29% for this group of patients. Peroperative complications were recorded in 50 patients (14%). Excessive bleeding (11%) and urinary tract injuries (3%) were most frequent. Postoperatively, 101 patients (28%) had some kind of complication associated with the surgical procedure. Surgical complications were more frequent among women over 50 years of age. Bladder dysfunction (11%) and obstruction of the ureter (8%) were recorded most frequently. In 19 cases (5.2%), urinary tract or intestinal fistulas were diagnosed during the period of follow-up. With increasing experience of the surgeons and fewer stage II tumors, the frequency of fistulas associated with the surgical procedure decreased to 2.4% during the latter part (1975-90) of the period. Adjunctive postoperative radiotherapy increased the risk of late complications. In 8 cases (6.4%), serious complications associated with the combination of surgery and radiotherapy were reported.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81389 (URN)
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
2. The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix
Open this publication in new window or tab >>The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix
Show others...
2002 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 1, 32-41 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to investigate the prognostic importance of clinical and histopathologic factors, including malignancy grading systems (MGS), partial index (PI), invasive front grading (IFG), and microvessel density. A complete geographic series of 172 early stage (FIGO I–II) cervical carcinomas treated by Wertheim-Meigs surgery during the period 1965–1990 was studied. The patients were followed up for at least 10 years. Significant prognostic factors for disease-free survival were lymph node status (P < 0.0000001), radical surgical margins (P = 0.00003), and tumor size (P = 0.008). In a multivariate Cox analysis it was shown that lymph node status was the single most important prognostic factor with regard to disease-free survival. The total MGS and the PI scores were highly significantly (P = 0.0001) associated with pelvic lymph node metastases and disease-free survival rate in squamous cell carcinomas. The MGS and the PI systems were superior to the IFG system in predicting lymph node metastases. The total IFG score was also a statistically highly significant (P = 0.003) prognostic factor with regard to disease-free survival in both univariate and multivariate analyses. Microvessel density was a nonsignificant prognostic factor. There was a highly significant (P = 0.002) association between vascular space invasion of tumor cells and the presence of lymph node metastases. In conclusion, histopathologic malignancy grading systems provide valuable prognostic information in patients with early stage squamous cell carcinomas of the uterine cervix.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81390 (URN)10.1046/j.1525-1438.2002.01075.x (DOI)
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
3. The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas
Open this publication in new window or tab >>The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas
2002 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 2, 149-157 p.Article in journal (Refereed) Published
Abstract [en]

This study evaluated the prognostic importance of a new grading system focusing on the invasive tumor front, DNA profile, and the proliferation marker MIB-1. A complete geographic series of 172 women treated with radical hysterectomy (Wertheim–Meigs) for FIGO stage I–II cervical carcinomas was the target population. The analyses were performed on 141 (82%) squamous cell carcinomas of the complete series. During the period of observation (mean 222 months), 17 recurrences (12.1%) were encountered. Prognostic factors for disease-free survival were lymph node status (P < 0.000001), radical surgical margins (P = 0.00004), and tumor size (P = 0.002). The complete score of the invasive front grading system (IFG), and the individual scores of two variables—pattern of invasion and host response—were all significantly (P = 0.002, P = 0.007, P = 0.0001) associated with pelvic lymph node metastases. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting lymph node metastases. The total IFG score was also a significant (P = 0.003) prognostic factor for disease-free survival. DNA ploidy, S-phase fraction, and MIB-1 expression were nonsignificant factors in predicting pelvic lymph node metastases and disease-free survival of the patient. The IFG in the original or modified versions could predict low- and high-risk groups of tumors and therefore be of value in treatment planning for these patients.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81392 (URN)10.1046/j.1525-1438.2002.01088.x (DOI)
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
4. Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma: Correlation with clinical outcome
Open this publication in new window or tab >>Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma: Correlation with clinical outcome
2002 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 3, 290-298 p.Article in journal (Refereed) Published
Abstract [en]

The objective of this study was to assess the value of p53, bcl-2, and p21WAF1/CIP1 immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21WAF1/CIP1. None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21WAF1/CIP1 appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81391 (URN)10.1046/j.1525-1438.2002.01113.x (DOI)
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
5. MIB-1, p53, bcl-2 and WAF-1 expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas: Correlation with clinical outcome
Open this publication in new window or tab >>MIB-1, p53, bcl-2 and WAF-1 expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas: Correlation with clinical outcome
(English)Manuscript (preprint) (Other academic)
Abstract [en]

A complete series of 40 cervical carcinomas with pelvic lymph node rnetastases were analysed immunohistochemically for prognostic markers. The aims of this study were to examine whether the detection of MIB-1, p53, bcl-2, and WAF-1 could be used as a prognostic marker for tumor recurrence and survival rate. During the period of observation (mean 222, range 72-360 months) 22 (55%) recurrences were encountered and 20 patients died of the disease. There were 35 squamous cell carcinomas (87.5%), 2 adenosquamouscarcinomas (5.0%), and 3 pure adenocarcinomas (7.5%). One tumor (2.5%) was well differentiated, 12 twnors (30%) were moderately differentiated, and 27 tumors (67 .5%) were poorly differentiated. The primary tumor grade (P=0.037) and radicality of the surgical margins (P=0.021) were significant prognostic factors with regard to tumor recurrence. The site and number of lymph nodes with metastases had no prognostic value. P53, bcl-2, and WAF-1 were not predictive factors for recurrences or the cancer-specific survival rate. The concordant expression of WAF-1 in the primary tumor and in lymphnode metastases was lower than for p53 and bcl-2. The proliferative activity (MIB-1) seemed to be lower in tumor cells metastasized to the pelvic lymph nodes than in cells of the primary tumor. Expression of MIB-1 in lymph nodes was predictive of disease-free survival in both univariate and mu!tivariate proportional hazard Cox analyses.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81393 (URN)
Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2012-09-13Bibliographically approved

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