Location of Repository

A study of the predictive value of morphometric assessments in clinical outcome in ovarian epithelial malignancy

By Julia Elizabeth Palmer

Abstract

Quantitative pathology as a tool in gynaecological pathology is fairly new. Such techniques allow greater objectivity than histological grading, typing, and residual tumour estimation. This study aims to determine: whether basic morphometry data can predict outcome and chemotherapeutic response, whether newer semi-automated methods of tumour morphometry provide similar results to older methods, and whether advanced image analysis methods can offer further tumour outcome data in ovarian carcinoma. The study was performed on a well-selected group of serous ovarian carcinomas. Tumour outcome, survival and chemotherapeutic response, were investigated in 132 patients treated with the same platinum containing regimes. Traditional clinicopathologic parameters, p53 & Bcl2, mitotic activity index (MAn and angiogenesis determinants were initially investigated. Semi-automated analysis, using immunohistochemically based techniques, were applied to estimate volume percentage epithelium (VPE) and nuclear morphometric parameters. Syntactic structure analysis including, minimum spanning tree, and neighbourhood features, was also investigated. Multivariate analysis revealed residual disease status, FIGO stage, MAl, VPE, equivalent nuclear diameter, and angiogenesis parameters to be strong prognosticators for overall and disease free survival. Residual disease status, VPE, nuclear length and angiogenesis parameters were found significant predictors of chemotherapy response. Angiogenesis parameters, as determined by semi-automated image analysis techniques, were found overall to be the strongest prognosticators. Morphometric data can predict outcome and chemotherapeutic response in ovarian serous carcinoma. Semi-automated morphometry techniques provide similar results to ()lder methods, and advanced image analysis can offer further outcome data. The rationale for the application of semi-automated and automated detection is that it may provide an unbiased sampling of a lesion and possibly a more representative estimate of areas that a human expert might label. Such determined, quantitative pathological findings were found to have important value in predicting prognosis in ovarian carcinoma and, if not to supersede, certainly to add to classical prognostic factors

Topics: RC0254
OAI identifier: oai:wrap.warwick.ac.uk:1158

Suggested articles

Preview

Citations

  1. (2000). A critique of surgical cytoreduction in advanced ovarian cancer. Gynecol Oncol
  2. (2004). A new prognostic model comprising p53, EGFR, and tumour grade in early stage epithelial ovarian carcinoma and avoiding the problem of inaccurate surgical staging.
  3. (1988). a prognostic and predictive factor in ovarian cancer.
  4. (1983). A radioirnmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer.
  5. (2000). A semi-automated method for determination of percentage tumour epithelium and M IB I count in ovarian epithelial turnours.
  6. (1993). Age as a prognostic factor in ovarian carcinoma. The gynecologic oncology group experience. Cancer
  7. (1994). An Assessment of the Value of Serum Ca125 Measurements in the management of epithelial ovarian carcinoma. Gynae Oncol
  8. (2005). An immunohistochernical comparison between low-grade and high-grade ovarian serous carcinomas.
  9. (2003). An original approach for the 211 quantification of blood vessels on the whole tumour section. Anal Cell Pathol
  10. (1993). Analysis of patient age as an independent prognostic factor for survival in a phase III study of cisplatin-cyclophosphamide versus carboplatin- cyclophosphamide in stages III (suboptimal) and IV ovarian cancer. A 187 southwest oncology group study. Cancer
  11. (1999). Angiogenesis in malignancies of the female genital tract. Gynecol Oncol
  12. (1997). Angiogenesis in primary and metastatic cpithelial ovarian carcinoma. AJOG
  13. (2002). Apoptotic bodies as morphological feature in serous ovarian carcinoma: correlation with nuclear grade,
  14. (1996). Application of attributed graphs in diagnostic pathology. Anal Quant Cytol Histol
  15. (1987). Application of morphometry in tumor pathology. Anal Quant Cytol Histol
  16. (1996). Association of vascular endothelial growth factor expression with intraturnoral microvessel density and tumour cell proliferation in human epidermoid lung carcinoma.
  17. (1997). Association of vascular endothelial growth factor expression with turnour cell proliferation in ovarian carcinoma. Anticancer Res
  18. (1991). Automated selection of the most epithelium-rich areas in gynaecologic tumour sections. Anal Quant Cytol Ifistol
  19. (1962). Autoradiographic analysis of cell proliferation in spontaneous breast 202 cancer of OH mouse. 111. The growth fraction.
  20. Baak JPA1991- Manual of quantitative pathology in cancer diagnosis and prognosis. I"
  21. (1996). BcI-2 expression, p53 accumulation and apoptosis in ovarian carcinomas.
  22. (2003). Bcl-2 down-regulation is a novel mechanism of paclitaxal resistance. Mol Phannacol
  23. (2003). Biological markers in pT1 and pT2 ovarian cancer with lymph node metastasis. Gynecol Oncol
  24. (2000). Brcsciani G ct al. p53 Gcne status and response to platinum/paclitaxal based chemotherapy in advanced ovarian carcinoma.
  25. (1992). CA 125 surveillance and second look laparotomy in ovarian carcinoma.
  26. (1987). Ca125 as a serum marker for poor prognosis in ovarian malignancy. Gynecol Oncol
  27. (1926). Carcinoma: grading and practical application. Arch Pathol
  28. (2006). CD31(PECAM-1) Immunohistochernical Staining Protocol. IFIC World [online], 1(1). Available at: http: //www.
  29. (1999). Chemosensitivity and p53-dependent apoptosis and epithelial ovarian 201 carcinoma. Cancer
  30. (1996). Clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy in stage HI disease. Gynecol Oncol
  31. Clinical and histologic studies of ovarian carcinoma: long-term follow-up of 990 cases..
  32. (1995). Clinical applications of research on angiogenesis.
  33. (1994). Clinical prognostic significance of turnour angiogenesis. Annals of oncology
  34. (1998). Clinical significance of (x-catenin, collagen IV and Ki67 expression in epithelial ovarian cancer. Clin Oncol
  35. (2000). Combined prognostic importance of Ca125, histopathologic grade and DNA index in advanced ovarian cancer.
  36. (1997). comparative study of spatial point pattern analysis 208 methods.
  37. Comparison of commercially available cytokeratin antibodies in normal and neoplastic adult epithelial and non-epithelial tissues.
  38. (2000). Complctc cytoreduction: Is epithelial ovarian cancer confined to the pelvis biologically different from bulky abdominal disease? Gynecol Oncol
  39. (1998). Complete cytoreductive surgery is feasible and maximises survival in patients with advanced epithelial. ovarian cancer: A prospective study. Gynecol Oncol
  40. computer-aided image analysis measurements of angiogenesis and their ability to predict chemotherapy response in serous carcinoma of the ovary. Palmer Julia E, Sant Cassia Louis
  41. (1999). Computer-assisted differential diagnosis of malignant mesotheliorna, based on syntactic structure analysis. Cytometry
  42. (1990). Consistcncy of quantitative methods in ovarian tumour histopathology.
  43. (1994). Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science
  44. (2004). Correlation between MlBl-determined tumor growth fraction and incidence of tumor recurrence in early ovarian carcinomas. Cancer Investigation
  45. (2001). Correlation of p53 mutations with resistance to platinum - based chemotherapy and shortened survival in ovarian cancer.
  46. (2004). COX-2 status in relation to tumor microvessel density and VEGF expression: Analysis in ovarian carcinoma patients with low versus high survival rates. Oncology Reports
  47. (1999). ct A Value of morphometry, texture analysis, densitometry, and histometry in the differcntial diagnosis and prognosis of malignant mesotheliorna.
  48. (1990). De Bruijn HWA. The effect of abdominal surgery on the serum concentration of the tumour associated antigen Ca125. BJOG
  49. (1996). Defining progression of ovarian carcinoma during follow-up according to Cal25: A North Thames ovary group study. Annals of Oncology
  50. (1993). Detection of the Ki67 antigen in fixed and wax-cmbeddcd sections with the monoclonal antibody MIBI. Histopathology
  51. (1993). Determination of proliferation index in advanced ovarian cancer using quantitative image analysis. AJCP
  52. (1994). Determination of proliferation index with MUB-I in advanced ovarian cancer using quantitative image analysis. AJCP
  53. (1996). Differences in risk factors for epithelial ovarian cancer by histologic type: results of a case control study.
  54. (2003). Distinct subtypes of serous ovarian carcinoma identified by p53 determination. Gynecol Oncol
  55. (1997). Does dcbulking surgery improve survival in biologically aggressive ovarian carcinoma? Gynccol Oncol
  56. (2002). Dunder 1, Ensari A, Cengiz SD. Prognostic value of p53 accumulation in epithelial ovarian carcinomas. Arch Gynecol Obstet
  57. (1990). Early serum Ca125 response and outcome in epithelial ovarian cancer.
  58. Endothelial cell markers CD31, CD34, and BNH9 antibody to H- and Y- antigens - evaluation of their specificity in the diagnosis of vascular turnours and comparison with von Willcbrand factor. Mod pathol 1994; 7(l):
  59. (1996). Epithclial ovarian turnours in the reproductive age group: Age is not an independent prognostic factor. Cancer
  60. (1999). Epithelial ovarian carcinoma in the reproductive age group. Cancer
  61. (1989). Evaluation of automated estimation of epithelial volume and its prognostic value in ovarian tumors. Lab Invest
  62. (2003). Evaluation of clinical significance of TP53, BCL-2, BAX and MEKI expression in 229 199 ovarian carcinomas treated with platinum-based regimen.
  63. (1995). Expression and prognostic significance of bcl-2 in ovarian turnours.
  64. (2006). Factor VHI Immunohistochernical Staining Protocol.
  65. (1985). Factors influencing survival in carcinoma of the ovary. Cancer
  66. (1995). Further evaluation of reproducibility and prognostic value of histologic typing and grading in FIGO stage I ovarian cancer patients without systemic loco-regional adjuvant chemotherapy.
  67. Glutathione S transferase GSTM I and GSTTI genotypes in ovarian cancer: Association with p53 expression and survival.
  68. (2001). Glutatione S-transferase GSMI and GSTTI genotypes in ovarian cancer: association with p53 expression and survival.
  69. Grading Ovarian Tumors: Evaluation of decision making by different pathologists. Anal Quant Cytol Histol 1986(Dec);
  70. Grading Ovarian Tumors: Evaluation of decision making by different pathologists. Anal Quant Cytol Histol 1986(Dec); 8(4);
  71. (2004). HER-2 over-expression is an independent marker of poor prognosis of advanced primary ovarian carcinoma: a multicenter study of the GINECO group. Annals of Oncology
  72. (2002). Heterogeneity of ovarian cancer: relationships among histological group, stage of disease, turnour markers, patient characteristics and survival. Cancer Invest
  73. (1985). Heyderman E, ct at. Production of monoclonal antibodies against human epithelial membrane antigen for use in diagnostic immunocytochernistry.
  74. (2005). Histologic types of epithelial 194 ovarian cancer: have they different risk factors? Gynecol Oncol
  75. How malignant is malignant? A brief review of the microscopic assessment of human neoplasms, and the prediction of whether they will metastasize and kill.
  76. (1989). Immunohistochernical determination of tumour growth fraction in human ovarian carcinoma. BJOG
  77. (1998). Immunophcnotypc of ovarian cancer as a predictor of clinical outcome: evaluation at primary surgery and second - look procedure. Gynecol Oncol
  78. (1982). Importance of histological grading in the prognosis of epithelial ovarian carcinoma. Obstet Gynecol
  79. (1998). Increased microvessel density in mucinous compared with malignant serous and benign turnours of the ovary.
  80. (1999). Increased mortality in postmenopausal women with serum Ca125 elevation.
  81. (1996). Influence of boundary effects on minimum spanning tree features. Anal Quant Cytol Histol
  82. (1994). Integrated optical density (IOD), syntactic structure analysis, and survival in operated lung carcinoma patients. Path Res Pract
  83. (1979). International Federation of Gynaecologists & Obstetricians cancer committee: Annual report on the results of treatment in gynaecological cancer.
  84. (1998). International Federation of Gynaecologists & Obstetricians Cancer Committee: Annual report on the results of treatment in gynaecological cancer. Vol 23.
  85. (1988). International Federation of Gynaecology and Obstetrics staging of endometrial cancer
  86. (1984). Interobserver Variability in the interpretation of Epithelial Ovarian Cancer. Gynaecologic Oncology
  87. (2002). Interval debulking surgery in advanced cpithclial ovarian cancer. Best Pract Res Clin Obstet Gynecol
  88. (1995). Intraturnor microvesel density as a prognostic factor in cancer. AJP
  89. (2003). Intraturnoral microvessel density, response to chemotherapy and clinical outcome of patients with advanced ovarian carcinoma. Anticancer Research
  90. Is Cal25 monitoring useful in patients with epithelial ovarian carcinoma and preoperative negative Ca125 serum levels.
  91. (1995). Ki67 antigen immunostaining (MlB I monoclonal antibody) in serous ovarian tumors: index of proliferative activity with prognostic significance. Gynecol Oncol
  92. (1996). Lack of improved survival plus increase in thromboembolic complications in patients with clear cell carcinoma of the 195 ovary treated with platinum versus non-platinum-based chemotherapy. Cancer
  93. (2002). Limited penetration of anticancer drugs through turnour tissue. Clin Cancer Res
  94. (2004). Long-term results of cytorccluctive surgery for advanced and recurrent epithelial, ovarian cancers and papillary serous carcinoma of the peritoneum.
  95. (1990). Method for the quantitative evaluation of the distribution pattern of nuclei in normal and malignant cndometrial epithelia. Anal Quant Cytol Histol
  96. (1997). Mib-I evaluated proliferative activity in ovarian cancer with respect to prognostic significance. Anticancer research
  97. (1995). Microvessel density quantification in breast carcinomas. Assessment by light microscopy vs a computer - aided image analysis system. Applied Immunohistochemistry
  98. (1995). Microvessel density, endothelial cell proliferation and tumour cell proliferation in human colorectal. adenocarcinomas.
  99. (1997). Minimum spanning tree analysis in advanced ovarian carcinoma. An investigation of sampling methods, reproducibility and correlation with histologic grade. Anal Quant Cytol Ifistol
  100. (1989). Minimum spanning tree, voronoi's tesselation and Johnson- Mehl diagrams in human lung carcinoma. Path Res Pract
  101. (1984). Monoclonal Antibody immunoradiometric assay for an antigenic determinant (Ca125) associated with human epithelial ovarian carcinomas. Cancer Research
  102. (1990). Monoclonal antibody Ki-67 : its use in histopathology. Hislopathology
  103. (1986). Morphometric data to FIGO stage and histological type and grade for prognosis of ovarian tumours.
  104. Morphometry in surgical pathology.
  105. (1996). Morpohmetric applications in anatomic pathology. Hum Pathol
  106. (1993). Muir's, textbook of pathology. 13 th edition.
  107. (1992). Multiparametric discrimination of serous ovarian turnours by analytical morphometry.
  108. (2000). Multiple births and risk of epithelial ovarian cancer.
  109. (1995). Mutant p53 protein overexpression is associated with poor outcome in patients with well or moderately differentiated ovarian carcinoma. Cancer
  110. (1994). National survey of ovarian carcinoma XH: epithelial ovarian malignancies in women less than or equal to 25 years of age. Cancer
  111. (1994). national survey of ovarian carcinoma. IV: Patterns of care and related survival for older patients. Cancer
  112. (1986). Neighbourhood analysis of low magnification structures (glands) in healthy adenomatous, and carcinomatous colon mucosa. Path Res Pract
  113. (1987). Neighbourhood condition and application of syntactic structure analysis in histopathology.
  114. (1993). Normalization of the minimum spanning tree. Anal Cell Pathol
  115. (1992). Nuclear morphometry: a strong prognostic factor for survival after secondary surgery in advanced ovarian cancer.
  116. (2004). Nuclear size, shape and density in endometrial carcinoma: relationship to survival at over 5 years of follow-up. Does analysing only cells occupying the GO-G I peak add useful information?
  117. (1992). Nuclear volume and prognosis in ovarian cancer.
  118. (2006). Ovarian Cancer Markers-BCL-2. Veripath Onco Diagnostics [online]. Available at:
  119. (2002). Ovarian Cancer p53 mutation is associated with tumor microvessel density. Gynecol Oncol
  120. (2005). Ovarian Cancer Statistics for the UK (online). Cancer Research UK. Available at http: //info. canceffesearchuk. org/cancerstats/types / ovary/? a5441>
  121. (1999). Ovarian cancer: should we be managing patients with good and bad prognostic factors in the same manner. Annals of Oncology
  122. Overexpression and mutation of p53 in epithelial ovarian cancer.
  123. (1992). Overexpression of the p53 protein and allele loss at 17p 13 in ovarian carcinoma.
  124. (1993). p53 accumulation in ovarian carcinomas and its prognostic implications. Hum Pathol
  125. (2000). p53 and bcl-2 in epithelial ovarian carcinoma: their value as prognostic indicators at a median follow-up of 60 months. Gynecol Oncol
  126. (1995). p53 cell cycle control and apoptosis: implications for cancer. Cancer and Metastasis Reviews
  127. (1994). p53 expression in epithelial ovarian neoplasms: relationship to clinical and pathological parameters; Ki67 expression and flow cytometry. Gynecol Oncol
  128. (1993). p53 gene mutations and protein accumulation in human ovarian cancer.
  129. (1992). p53 Overexpression in formalin-fixed, paraffin-embedded tissue detected by immunohistochemistry. Jounial Histochem Cytochein
  130. (1996). p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer. Gynecol Oncol
  131. (1995). p53 protein detected by HiC as a prognostic factor in patients with epithelial ovarian cancer. Cancer
  132. p53, bCI-2 and bax: Their relationship and effect on prognosis in early stage epithelial ovarian carcinoma.
  133. (2005). Patterns of p53 mutations separate ovarian serous borderline turnours and lowand high-grade carcinomas and provide support for a new model of ovarian carcinogenesis: a mutational analysis with immunohistochernical correlation.
  134. (2002). Perrett CW Angiogenesis in epithelial ovarian cancer. Mol Pathol
  135. (1991). Pre-chemotherapy serum Ca125 level as a predictor of survival outcome in epithelial carcinoma of the ovary. Clin Oncol
  136. (1988). Prediction of long-term survival by flow cytometric analysis of cellular DNA content in patients with advanced ovarian cancer.
  137. (2004). Predictive factors for irresectability in advanced ovarian cancer.
  138. (1996). Predictive value of proliferative cellular nuclear antigen (PCNA) and Ki67 antigen in advanced stage serous 203 papilliferous ovarian cancer.
  139. (1987). Predictive value of serial Ca125 antigen levels in ovarian cancer evaluated by second-look laparotomy.
  140. (1995). Predictive value of the combination of serum markers Ca125, CASA, and TPS in ovarian cancer.
  141. (1995). Preoperative Ca125: An independent prognostic factor in patients with stage I epithelial ovarian cancer. Obstet Gynecol
  142. (2001). Preoperative Cal25 level as a predictor of non-optimal cyto-reduction of advanced epithelial ovarian cancer. Acta Obstet Gynecol Scand
  143. (1977). Primary epithelial tumours of the ovary.
  144. (2004). Prognostic 213 significance of microvessel density and vascular endothelial. growth factor expression in advanced ovarian serous carcinoma.
  145. (1996). Prognostic and predictive value of turnour angiogenesis in ovarian carcinomas.
  146. (1990). Prognostic factors in advanced epithelial ovarian cancer.
  147. (1987). Prognostic factors in borderline and invasive ovarian tumours of the common epithelial type. Path Res Pract
  148. (1983). Prognostic factors in malignant epithelial ovarian tumours. Gynecol Oncol
  149. (2001). Prognostic factors of stage IV epithelial ovarian cancer: A multicenter retrospective study. Gynecol Oncol
  150. (1999). Prognostic relevance of the endothelial marker CD34 in ovarian cancer. Anticancer Research
  151. (1984). Prognostic significance of histologic classification and grading of epithelial malignancies of the ovary. AJOG
  152. (2003). Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: 200 A Gynecologic Oncology Group Study J Clin Oncol
  153. (1990). Prognostic significance of tumor cell morphometry, histopathology, and clinical parameters in advanced ovarian carcinoma.
  154. (2004). Prognostic significance of turnour angiogenesis in epithelial ovarian cancer: in association with transforming growth factor B and VEGF.
  155. (1999). Prognostic significance of turnour angiogenesis in epithelial ovarian cancer. Cancer Lett
  156. (2000). Prognostic value of Ca125 kinetics and half-life in advanced cancer.
  157. Prognostic value of measurements of angiogenesis in serous carcinoma of the ovary. Palmer JE, Sant Cassia U, Irwin C, Morris AG2, Rollason TP.
  158. (1995). Prognostic value of microvessel quantitation
  159. (1999). Prognostic value of nuclear morphometry in patients with TNM stage TI ovarian clear cell adenocarcinorna.
  160. (1990). Prognostic value of ovarian carcinoma grading methods -a method comparison study. Histopathology
  161. (1996). Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation.
  162. (1989). Quantirication of cpithelial area by image processing applied to endometrial carcinomas: a comparison with ovarian tumors. Hum Palhol
  163. (1994). Quantitative pathologic features as predictors of long-term survival in patients with advanced ovarian cancer treated with cisplatin.
  164. (1998). Quantitative prognostic features in FIGO I ovarian cancer patients without postoperative treatment. Gynecol Oncol
  165. Reactivity of a monoclonal antibody with human ovarian carcinoma.
  166. (1997). Relationship between lifetime ovulatory cycles and over-expression of mutant p53 in epithelial ovarian cancer.
  167. (1991). Reproducibility of histopathological evaluation in epithelial ovarian carcinoma. Clinical implications. APMIS
  168. (2001). Reproduction-related risk factors for mucinous and non-mucinous epithelial ovarian cancer.
  169. (2003). Reproductive factors and epithelial ovarian cancer risk by histologic type: a multiethnic case control study.
  170. (2003). Results of interval debulking surgery compared with primary debulking 190 surgery in advanced stage ovarian cancer. JAm Coll Surg
  171. (2003). Results of interval debulking surgery in advanced stage ovarian cancer: an exposed - non-exposed study. Annals of Oncology
  172. (2000). Role of tumour markers in monitoring epithelial ovarian cancer.
  173. (1998). Scoazec JY. CD31 expression in benign, borderline, and malignant epithelial ovarian tumors: An Immunohistochernical and Serological Analysis. Gynecol Oncol
  174. (2002). Secondary cytoreductive surgery for recurrent epithelial ovarian cancer. Obstet Gynecol
  175. (1991). Serological monitoring of epithelial ovarian cancer disease markers.
  176. Significance of tumor marker determinations in the primary treatment of ovarian cancer. Anticancer Res 1997; 17(4B): 2949-5 I.
  177. (2005). Specification sheet Monoclonal Mouse Anti-Human BCL-2 Oncoprotein. Dako [online]. Available at: http: H www.
  178. (2005). Specification sheet Monoclonal Mouse Anti-Hurnan Cytokeratin. Dako [online]. Available at: URL: http: //www. dako-co. uk/prod-downloadpackageinsert pdf? objectid= 102466001
  179. (2005). Specification sheet Monoclonal Mouse Anti-Hurnan Epithclial Membrane Antigen. Dako [online]. Available at: URL:
  180. (1993). Spectrum of mutation and frequency of allelic gene deletion of the p53 gene in ovarian cancer.
  181. (2003). Stages III and IV invasive epithelial ovarian carcinoma in younger versus older women: What prognostic factors are important? Obstet Gynecol
  182. (1969). Stereological principles for morphometry in electron microscopy. Int Rev Cytol
  183. (1990). Steroid receptors and Ki-67 reactivity in ovarian cancer and in normal ovary. Correlation with DNA flow cytometry. Biochemical receptor assay, and patient survival.
  184. (1999). Study of borderline and invasive mucinous ovarian turnours using
  185. (1981). Surgery for common epithelial turnours of the ovary. Cancer
  186. (1997). Surgical pathology of the ovaries. 2 nd
  187. (1975). Surgical resection of tumour bulk in the primary treatment of ovarian carcinoma.
  188. (2003). Survival and prognostic factors in patients with ovarian cancer. Obstet Gynecol
  189. (2002). Survival effect of maximal cytoreductive surgery for advanced ovarian cancer during the platinum era: A meta analysis.
  190. (1992). Syntactic structure analysis in invasive breast cancer: analysis of reproducibility, biologic background, and prognostic value. Man Pathol
  191. (1994). Syntactic structure analysis in uveal melanomas.
  192. (1992). Syntactic structure analysis of the arrangement of dysplastic epithelium of colorectal adenomatous polyps. Anal Quant Cytol Histol
  193. (2001). Telornerase activity and p53 dependcnt apoptosis in ovarian cancer cells.
  194. (1993). Testing the validity of a prognostic classification in paticnts with surgically optimal ovarian carcinoma: a 15 year review.
  195. (1986). The Ca125 assay as a predictor of clinical recurrence in epithelial ovarian cancer. Obstet Gynecol
  196. (2002). The combined evaluation of p27 and Ki-67 expression provides independent information on overall survival of ovarian cancer patients Gynecol Oncol
  197. (1997). The combined evaluation of p53 accumulation and of Ki-67 (ME31) labelling index provides independent information on overall survival of ovarian cancer patients. Annals of Oncology
  198. (1995). The control of apoptosis and drug resistance in ovarian cancer: influence of p53 and bcl-2. Oncogene
  199. (2002). The effect of ascites, mass volume, and peritoneal carcinomata serum Ca125 levels in patients with ovarian carcinoma.
  200. (1995). The histologic grading of cancer. Cancer
  201. (1992). The influence of cytoreductive surgery on recuffence-free interval and survival in small volume stage III epithelial ovarian cancer: a gynaecologic oncology group study. Gynecol Oncol
  202. (2003). The influence of microvessel density on ovarian carcinogenesis. Gynecol Oncol
  203. (1979). The pathological assessment of ovarian neoplasms III: The malignant 'epithelial' tumours. Pathology
  204. (2002). The place of bowel resection in initial debulking surgery for advanced ovarian cancer.
  205. (1999). The prognostic 210 significance of angiogenesis in epithelial ovarian carcinoma. Clin Cancer Res
  206. The prognostic and predictive value of mitotic activity index and volume percentage epithelial estimates in serous ovarian carcinoma.
  207. The prognostic and predictive value of syntactic structure analysis in serous carcinoma of the ovary. Palmer JE, Sant Cassia
  208. (2002). The prognostic importance of p53, bcl-2 and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy.
  209. (1996). The prognostic significance of bcl-2 and p53 expression in ovarian carcinoma.
  210. (1999). The prognostic significance of p53 expression quantitated by computerized image analysis in epithelial ovarian cancer.
  211. (1995). The prognostic significance of residual disease, FIGO substage, turnour histology and grade in patients with FIGO stage III ovarian cancer. Gynecol Oncol
  212. (1991). The prognostic value of image analysis in ovarian cancer. Cancer
  213. (1985). The prognostic value of morphornetry in ovarian epithelial turnours of borderline malignancy.
  214. The prognostic value of nuclear morphometric analysis in serous ovarian carcinoma. Palmer JE, Sant Cassia
  215. (1993). The prognostic value of serum Ca125 in patients with advanced ovarian carcinoma: an analysis of 575 patients by the medical research council working party on gynaecological cancer.
  216. (1988). The prognostic value of the serum Half-Life of CA125 during induction chemotherapy. Gynecologic Oncology
  217. (2005). The relationship of molecular markers of p53 function and angiogenesis to prognosis of stage I epithelial ovarian cancer. Clin Cancer Res
  218. (1997). The role of CA-125 in the management of ovarian cancer. The Oncologist
  219. (1990). The role of Ca125 in the early diagnosis of progressive disease in ovarian cancer. Annals of Oncology
  220. (1995). The significance of differences in prognostic value of quantitative pathologic features in FIGO stage III and IV serous adenocarcinorna of the ovary between a group of Danish patients and other groups.
  221. (1989). The value of morphometry to predict chemotherapy response in advanced ovarian cancer. Path Res Pract.
  222. Thrombospondin-1 expression in epithelial ovarian carcinoma. Association with p53 ststus, tumor angiogenesis, and survival in platinum-treated patients.
  223. (1987). TNM stage, immuno-histology, syntactic structure analysis and survival in patients with small cell anaplastic carcinoma of the lung.
  224. (1998). Toward the development of a universal grading system for ovarian epithelial carcinoma: testing of a proposed system in a series of 461 patients with uniform treatment and follow-up. Cancer
  225. (1997). Tumor markers in ovarian cancer. The Oncologist
  226. Tumour angiogenesis and metastasis -correlation in invasive breast carcinoma.
  227. (1997). Tumour angiogenesis as a prognostic factor in ovarian carcinoma. Cancer
  228. (1972). Tumour Angiogenesis: A quantitative method for histologic grading.
  229. Tumour markers and ovarian cancer screening.
  230. (1934). Tumours of the female pelvic organs.
  231. (2000). Turnour angiogenesis and thymidine phosphorylase expression in ovarian carcinomas including serous surface papillary adenocarcinoma of the peritoneum.
  232. (1995). Turnour Angiogenesis in advanced stage ovarian carcinoma.
  233. (1995). Vlachonikolis 1, Delides GS. The prognostic value of morphometry in advanced epithelial ovarian cancers.
  234. (1995). Volume-weighted mean nuclear volume and nuclear area in advanced ovarian carcinoma. Anal Quant Cytol Histol
  235. (2001). What are the current surgical objectives, strategies and technical capabilities of gynaecologic: oncologists treating advanced epithelial ovarian cancer? Gynecol Oncol
  236. (1990). What is the evidence that turnours are angiogenesis dependent?
  237. (1995). Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression. Cancer Res
  238. (1996). Yang Yordan EL. Angiogenesis factor in endometrial carcinoma: a new prognostic indicator? AJOG

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.