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. 1997 Dec;50(6):304–309. doi: 10.1136/mp.50.6.304

Microvessel density, p53 overexpression, and apoptosis in invasive breast carcinoma.

F Gonzalez-Palacios 1, M Sancho 1, J C Martinez 1, C Bellas 1
PMCID: PMC379664  PMID: 9536280

Abstract

AIM: To investigate the possibility of a correlation among microvessel density, p53 overexpression, and apoptosis in invasive breast carcinoma. METHODS: Microvessel density was analysed in 105 cases of invasive breast carcinoma by immunohistology using antifactor VIII related antibody. The results were correlated with the immunohistochemical expression of p53 and the apoptotic index, detected using the in situ end labelling of fragmented DNA method (TUNEL). Assessment was made with a CAS 200 image analyser. All these studies were performed on formalin fixed, paraffin wax embedded tissue sections of tumour samples. RESULTS: The mean (SD) microvessel count was 47.2 (51.1), with a range from 7 to 250. Thirty five (33%) carcinomas showed overexpression of p53 protein. The apoptotic index of tumours ranged from 0.0 to 28.0, with a mean (SD) of 1.7 (3.2). The results showed that there was a significant inverse correlation between microvessel density and p53 expression (p = 0.04; odds ratio, 0.37). In contrast, no correlation was identified between the microvessel density and apoptotic index. CONCLUSIONS: These results suggest that in invasive breast carcinoma the p53 overexpression phenotype downregulates tumour neoangiogenesis, as does the wild-type of p53 protein. In addition, they suggest that apoptosis and neoangiogenesis in these tumours are independent processes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Axelsson K., Ljung B. M., Moore D. H., 2nd, Thor A. D., Chew K. L., Edgerton S. M., Smith H. S., Mayall B. H. Tumor angiogenesis as a prognostic assay for invasive ductal breast carcinoma. J Natl Cancer Inst. 1995 Jul 5;87(13):997–1008. doi: 10.1093/jnci/87.13.997. [DOI] [PubMed] [Google Scholar]
  2. Bosari S., Lee A. K., DeLellis R. A., Wiley B. D., Heatley G. J., Silverman M. L. Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol. 1992 Jul;23(7):755–761. doi: 10.1016/0046-8177(92)90344-3. [DOI] [PubMed] [Google Scholar]
  3. Brawer M. K. Quantitative microvessel density. A staging and prognostic marker for human prostatic carcinoma. Cancer. 1996 Jul 15;78(2):345–349. doi: 10.1002/(SICI)1097-0142(19960715)78:2<345::AID-CNCR25>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
  4. Charpin C., Devictor B., Bergeret D., Andrac L., Boulat J., Horschowski N., Lavaut M. N., Piana L. CD31 quantitative immunocytochemical assays in breast carcinomas. Correlation with current prognostic factors. Am J Clin Pathol. 1995 Apr;103(4):443–448. doi: 10.1093/ajcp/103.4.443. [DOI] [PubMed] [Google Scholar]
  5. Charpin C., Garcia S., Bouvier C., Andrac L., Devictor B., Lavaut M. N., Allasia C., Bonnier P., Piana L. Quantitative immunocytochemical assays on frozen sections of p53: correlation to the follow-up of patients with breast carcinomas. Am J Clin Pathol. 1996 Nov;106(5):640–646. doi: 10.1093/ajcp/106.5.640. [DOI] [PubMed] [Google Scholar]
  6. Costello P., McCann A., Carney D. N., Dervan P. A. Prognostic significance of microvessel density in lymph node negative breast carcinoma. Hum Pathol. 1995 Nov;26(11):1181–1184. doi: 10.1016/0046-8177(95)90190-6. [DOI] [PubMed] [Google Scholar]
  7. Craft P. S., Harris A. L. Clinical prognostic significance of tumour angiogenesis. Ann Oncol. 1994 Apr;5(4):305–311. doi: 10.1093/oxfordjournals.annonc.a058829. [DOI] [PubMed] [Google Scholar]
  8. Dameron K. M., Volpert O. V., Tainsky M. A., Bouck N. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science. 1994 Sep 9;265(5178):1582–1584. doi: 10.1126/science.7521539. [DOI] [PubMed] [Google Scholar]
  9. Dumont A. E. Factor VIII-related antigen. J Natl Cancer Inst. 1993 Apr 21;85(8):674–676. doi: 10.1093/jnci/85.8.674. [DOI] [PubMed] [Google Scholar]
  10. Elston C. W., Ellis I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x. [DOI] [PubMed] [Google Scholar]
  11. Fidler I. J., Ellis L. M. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell. 1994 Oct 21;79(2):185–188. doi: 10.1016/0092-8674(94)90187-2. [DOI] [PubMed] [Google Scholar]
  12. Folkman J. The role of angiogenesis in tumor growth. Semin Cancer Biol. 1992 Apr;3(2):65–71. [PubMed] [Google Scholar]
  13. Folkman J. Tumor angiogenesis and tissue factor. Nat Med. 1996 Feb;2(2):167–168. doi: 10.1038/nm0296-167. [DOI] [PubMed] [Google Scholar]
  14. Fontanini G., Bigini D., Vignati S., Basolo F., Mussi A., Lucchi M., Chine S., Angeletti C. A., Harris A. L., Bevilacqua G. Microvessel count predicts metastatic disease and survival in non-small cell lung cancer. J Pathol. 1995 Sep;177(1):57–63. doi: 10.1002/path.1711770110. [DOI] [PubMed] [Google Scholar]
  15. Gasparini G., Harris A. L. Clinical importance of the determination of tumor angiogenesis in breast carcinoma: much more than a new prognostic tool. J Clin Oncol. 1995 Mar;13(3):765–782. doi: 10.1200/JCO.1995.13.3.765. [DOI] [PubMed] [Google Scholar]
  16. Gasparini G., Weidner N., Bevilacqua P., Maluta S., Dalla Palma P., Caffo O., Barbareschi M., Boracchi P., Marubini E., Pozza F. Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J Clin Oncol. 1994 Mar;12(3):454–466. doi: 10.1200/JCO.1994.12.3.454. [DOI] [PubMed] [Google Scholar]
  17. Gasparini G., Weidner N., Maluta S., Pozza F., Boracchi P., Mezzetti M., Testolin A., Bevilacqua P. Intratumoral microvessel density and p53 protein: correlation with metastasis in head-and-neck squamous-cell carcinoma. Int J Cancer. 1993 Nov 11;55(5):739–744. doi: 10.1002/ijc.2910550507. [DOI] [PubMed] [Google Scholar]
  18. Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Goulding H., Abdul Rashid N. F., Robertson J. F., Bell J. A., Elston C. W., Blamey R. W., Ellis I. O. Assessment of angiogenesis in breast carcinoma: an important factor in prognosis? Hum Pathol. 1995 Nov;26(11):1196–1200. doi: 10.1016/0046-8177(95)90193-0. [DOI] [PubMed] [Google Scholar]
  20. Harris C. C., Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med. 1993 Oct 28;329(18):1318–1327. doi: 10.1056/NEJM199310283291807. [DOI] [PubMed] [Google Scholar]
  21. Harrison D. J. Counting apoptosis-why and how? Clin Mol Pathol. 1996 Oct;49(5):M245–M246. doi: 10.1136/mp.49.5.m245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Holmgren L., O'Reilly M. S., Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995 Feb;1(2):149–153. doi: 10.1038/nm0295-149. [DOI] [PubMed] [Google Scholar]
  23. Horak E. R., Leek R., Klenk N., LeJeune S., Smith K., Stuart N., Greenall M., Stepniewska K., Harris A. L. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet. 1992 Nov 7;340(8828):1120–1124. doi: 10.1016/0140-6736(92)93150-l. [DOI] [PubMed] [Google Scholar]
  24. Hurlimann J., Chaubert P., Benhattar J. p53 Gene alterations and p53 protein accumulation in infiltrating ductal breast carcinomas: correlation between immunohistochemical and molecular biology techniques. Mod Pathol. 1994 May;7(4):423–428. [PubMed] [Google Scholar]
  25. Leon S. P., Folkerth R. D., Black P. M. Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer. 1996 Jan 15;77(2):362–372. doi: 10.1002/(SICI)1097-0142(19960115)77:2<362::AID-CNCR20>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
  26. Marchetti A., Buttitta F., Pellegrini S., Campani D., Diella F., Cecchetti D., Callahan R., Bistocchi M. p53 mutations and histological type of invasive breast carcinoma. Cancer Res. 1993 Oct 1;53(19):4665–4669. [PubMed] [Google Scholar]
  27. Miliaras D., Kamas A., Kalekou H. Angiogenesis in invasive breast carcinoma: is it associated with parameters of prognostic significance? Histopathology. 1995 Feb;26(2):165–169. doi: 10.1111/j.1365-2559.1995.tb00647.x. [DOI] [PubMed] [Google Scholar]
  28. Ogawa Y., Chung Y. S., Nakata B., Takatsuka S., Maeda K., Sawada T., Kato Y., Yoshikawa K., Sakurai M., Sowa M. Microvessel quantitation in invasive breast cancer by staining for factor VIII-related antigen. Br J Cancer. 1995 Jun;71(6):1297–1301. doi: 10.1038/bjc.1995.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Simpson J. F., Page D. L. Status of breast cancer prognostication based on histopathologic data. Am J Clin Pathol. 1994 Oct;102(4 Suppl 1):S3–S8. [PubMed] [Google Scholar]
  30. Soong R., Robbins P. D., Dix B. R., Grieu F., Lim B., Knowles S., Williams K. E., Turbett G. R., House A. K., Iacopetta B. J. Concordance between p53 protein overexpression and gene mutation in a large series of common human carcinomas. Hum Pathol. 1996 Oct;27(10):1050–1055. doi: 10.1016/s0046-8177(96)90282-8. [DOI] [PubMed] [Google Scholar]
  31. Srivastava A., Laidler P., Hughes L. E., Woodcock J., Shedden E. J. Neovascularization in human cutaneous melanoma: a quantitative morphological and Doppler ultrasound study. Eur J Cancer Clin Oncol. 1986 Oct;22(10):1205–1209. doi: 10.1016/0277-5379(86)90322-6. [DOI] [PubMed] [Google Scholar]
  32. Srivastava S., Zou Z. Q., Pirollo K., Blattner W., Chang E. H. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature. 1990 Dec 20;348(6303):747–749. doi: 10.1038/348747a0. [DOI] [PubMed] [Google Scholar]
  33. Takebayashi Y., Aklyama S., Yamada K., Akiba S., Aikou T. Angiogenesis as an unfavorable prognostic factor in human colorectal carcinoma. Cancer. 1996 Jul 15;78(2):226–231. doi: 10.1002/(SICI)1097-0142(19960715)78:2<226::AID-CNCR6>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  34. Toi M., Kashitani J., Tominaga T. Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma. Int J Cancer. 1993 Sep 30;55(3):371–374. doi: 10.1002/ijc.2910550305. [DOI] [PubMed] [Google Scholar]
  35. Traweek S. T., Kandalaft P. L., Mehta P., Battifora H. The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia. Am J Clin Pathol. 1991 Jul;96(1):25–31. doi: 10.1093/ajcp/96.1.25. [DOI] [PubMed] [Google Scholar]
  36. Van Hoef M. E., Knox W. F., Dhesi S. S., Howell A., Schor A. M. Assessment of tumour vascularity as a prognostic factor in lymph node negative invasive breast cancer. Eur J Cancer. 1993;29A(8):1141–1145. doi: 10.1016/s0959-8049(05)80304-1. [DOI] [PubMed] [Google Scholar]
  37. Vermeulen P. B., Roland L., Mertens V., Van Marck E., De Bruijn E. A., Van Oosterom A. T., Dirix L. Y. Correlation of intratumoral microvessel density and p53 protein overexpression in human colorectal adenocarcinoma. Microvasc Res. 1996 Mar;51(2):164–174. doi: 10.1006/mvre.1996.0018. [DOI] [PubMed] [Google Scholar]
  38. Weidner N., Carroll P. R., Flax J., Blumenfeld W., Folkman J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol. 1993 Aug;143(2):401–409. [PMC free article] [PubMed] [Google Scholar]
  39. Weidner N., Folkman J., Pozza F., Bevilacqua P., Allred E. N., Moore D. H., Meli S., Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992 Dec 16;84(24):1875–1887. doi: 10.1093/jnci/84.24.1875. [DOI] [PubMed] [Google Scholar]
  40. Weidner N. Tumor angiogenesis: review of current applications in tumor prognostication. Semin Diagn Pathol. 1993 Nov;10(4):302–313. [PubMed] [Google Scholar]
  41. Wu J. Apoptosis and angiogenesis: two promising tumor markers in breast cancer (review). Anticancer Res. 1996 Jul-Aug;16(4B):2233–2239. [PubMed] [Google Scholar]
  42. Wynford-Thomas D. P53 in tumour pathology: can we trust immunocytochemistry? J Pathol. 1992 Apr;166(4):329–330. doi: 10.1002/path.1711660402. [DOI] [PubMed] [Google Scholar]
  43. Yoshino S., Kato M., Okada K. Prognostic significance of microvessel count in low stage renal cell carcinoma. Int J Urol. 1995 Jul;2(3):156–160. doi: 10.1111/j.1442-2042.1995.tb00445.x. [DOI] [PubMed] [Google Scholar]

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