| 1. |
- Bohr Mordhorst, Louise, 1958-
(författare)
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Predictive and prognostic factors in cervical carcinomas treated with (chemo-) radiotherapy
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A series of 131 women with cervical carcinoma FIGO stage I-IV were treated with external radiotherapy and intracavitary brachytherapy. In 47 patients (36%) concomitant chemotherapy was given. One hundred and twenty-one tumors (92%) achieved complete remission. Addition of chemotherapy increased primary cure rate to 98%. Tumor stage, tumor size, and histology were significant predictive factors for primary cure. Treatment related factors were: brachytherapy dose and interruption of irradiation.Thirty-nine recurrences (30%) were recorded. Tumor stage, histology, and concomitant chemotherapy were significant predictive factors.The 5-year cancer-specific survival rate of the complete series was 65%. Tumor size was a strong prognostic factor in multivariate analysis.Serum samples from 44 patients were analyzed. Ten candidate biomarker proteins with regard to tumor recurrences were identified.Five Hedgehog proteins were analyzed with immunohistochemistry. Residual tumor, local and distant recurrences and survival rate were associated with PTCH, SMO and GLI2. In the Wnt-β-catenin study intense staining of the membranes and nuclear staining > 5% were of significant predictive and prognostic value. Intense nuclear APC staining was associated with recurrences and cancer-specific survival rate.Conclusion: Histology, tumor size and brachytherapy dose were important clinical predictive and prognostic factors. Multiprotein analysis identified ten biomarker proteins associated with tumor recurrences. Three proteins (PTCH, SMO, and GLI2) in the Hedgehog pathway were of predictive and prognostic value. In the Wnt-β-catenin pathway intensity of β-catenin membrane staining and accumulation in the nuclei as well as nuclear APC-expression were of predictive and prognostic value.
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| 2. |
- Graflund, Marianne
(författare)
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Prognostic Factors in Early Stage Cervical Carcinomas Treated with Wertheim-Meigs Surgery
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 3. |
- Ranhem, Cecilia, et al.
(författare)
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Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma
- 2022
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Primary vaginal cancer (PVC) is a rare gynae- cological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prog- nosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was signifi- cantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.
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| 4. |
- Rosenberg, Per
(författare)
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On the prognosis and treatment of early stage endometrial carcinoma : Studies with special reference to uterine papillary serous carcinoma
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prognosis and therapy in the subgroup of endometrial malignancies called Uterine Papillary Serous Carcinoma (UPSC) was investigated. This entity constitutes about 6-8 % of all endometrial carcinomas clinical stage I but, as has been shown here, accounts for one third of the cancer mortality in the early stages of endometrial carcinoma.-The prognostic significance of nuclear atypia, FIGO grade and age was determined in patients with clinical stage 1-11 Uterine Papillary Serous Carcinoma.-DNA-index and S-phase fraction, determined by flow cytometry on formalin-fixed, paraffin-embedded endometrial curettage material was evaluated in relation to nuclear atypia, FIGO grade and age in early stage endometrial carcinoma.-A new method of minimizing the dilution of non-epithelial cells in the malignant curettage material when performing flow cytometry was developed.-The survival and pattern of metastasis in a population-based patient material was investigated -The effects on survival of a new aggressive treatment regimen was assessed.The results show that: Patients with uterine papillary serous carcinoma have a much worse prognosis than do patients with ordinary endometrial carcinoma.DNA ploidy and S-phaseratederived from flow cytometryperformed on disintegrated, previously paraffinembedded, endometrial curettings are important prognostic factors.It is possible to exclude contaminating non-epithelial cells from the DNA analysis by the use of an anticytokeratin antibody, Patients with uterine papillary serous carcinoma clinical stage I have a significantly higher risk of recurrence than patients with non-UPSC. The localisation of the recurrences among the UPSC patients is more similar to that of serous papillary ovarian carcinoma than that of ordinary adenocarcinoma of the endometrium. A primary treatment ofUPSC with a more extensive surgery, adjuvant external radiation and platinum-based chemotherapy seems to improve the outcome.
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