Summary
Assessment of tumour vascularity in core biopsy specimens may be a useful predictor of response to primary therapy. This study addresses practical methodological issues regarding accuracy of tumour vascularity assessments in different breast cancer specimens. Issues addressed in the study are variation caused by (i) inherent observer variation in the method, (ii) tumour heterogeneity and (iii) previous surgical manipulation of tumours. Microvessel counts were performed by two observers on separate occasions and by two different observers. Counts were performed on core biopsies and tumour sections taken simultaneously (n = 16) and with an intervening time interval (n = 21). In addition core biopsies were obtained from the same tumour on two separate occasions (n = 10). A highly significant correlation was found in counts performed by the same observers at different times and between two different observers. No significant correlation was found in counts of core biopsies and tumour sections taken either simultaneously or subsequently. No correlation was found between counts of sequential core biopsies. Study findings suggest that, although microvessel counts may be assessed reproducibly by the same and different observers, counts performed in core biopsies do not accurately reflect those of overall tumour, limiting their potential as predictive or prognostic markers.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Axelsson, K, Ljung, EB-M, Moore, DHII, Thor, AD, Chew, KL, Edgerton, SM, Smith, HS & Mayall, BH (1995). Tumor angiogenesis as a prognostic assay for invasive ductal breast carcinoma. J Natl Cancer Inst 87: 997–1008.
Bergers, E, van Diest, PJ & Baak, JP (1996). Tumour heterogeneity of cell cycle variables in breast cancer measured by flow cytometry. J Clin Pathol 49: 931–937.
Cordell, JL, Falini, B, Erber, WN, Ghish, AK, Abdulaziz, Z, MacDonald, S, Pulford, KA, Stein, H & Mason, DY (1984). Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32: 219–229.
Costello, P, McCann, A, Carney, DN & Dervan, PA (1995). Prognostic significance of microvessel density in lymph node negative breast carcinoma. Hum Pathol 26: 1181–1184.
Daidone, MG, Orefice, S, Mastore, M, Santoro, G, Salvadori, B & Silvestrini, R (1991). Comparing core needle to surgical biopsies in breast cancer for cell kinetics and ploidy studies. Breast Cancer Res Treat 19: 33–37.
de Jong, JS, van Diest, DJ & Baak, JP (1995). Heterogeneity and reproducibility of microvessel counts in breast cancer. Lab Invest 73: 922–926.
Folkman, J (1971). Tumour angiogenesis: therapeutic implications. N Engl J Med 285: 1182–1186.
Folkman, J (1990). What is the evidence that tumors are angiogenesis dependent? (editorial). J Natl Cancer Inst 82: 4–6.
Folkman, J (1994). Angiogenesis and Breast Cancer (editorial). J Clin Oncol 12: 441–443.
Fox, SB, Leek, RD, Weekes, MP, Whitehouse, RM, Gatter, KC & Harris, AL (1995). Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol 177: 275–283.
Gasparini, G, Weidner, N, Bevilacqua, P, Maluta, S, Dalla Palma, P, Caffo, O, Barbareschi, M, Boracchi, P, Marubini, E & Pozza, F (1994). Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J Clin Oncol 12: 454–466.
Hansen, S, Grabau, DA, Rose, C, Bak, M & Sorensen, FB (1998). Angiogenesis in breast cancer: a comparative study of the observer variability of methods for determining microvessel density. Lab Invest 78: 1563–1573.
Horak, ER, Leek, R, Klenk, N, LeJeune, S, Smith, K, Stuart, N, Greenall, M, Stepniewska, K & Harris, AL (1992). Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet 340: 1120–1124.
Jacobs, TW, Siziopikou, KP, Prioleau, JE, Raza, S, Baum, JK, Hayes, DF & Schnitt, SJ (1998). Do prognostic marker studies on core needle biopsy specimens of breast carcinoma accurately reflect the marker status of the tumour? Modern Pathol 11: 259–264.
Jannink, I, Risberg, B, Van Diest, PJ & Baak, JP (1996). Heterogeneity of mitotic activity in breast cancer. Histopathology 29: 421–428.
Jensen, V & Ladekarl, M (1995). Immunohistochemical quantitation of oestrogen receptors and proliferative activity in oestrogen receptor positive breast cancer. J Clin Pathol 48: 429–432.
Martin, L, Green, B, Renshaw, C, Lowe, D, Rudland, P, Leinster, SJ & Winstanley, J (1997a). Examining the technique of angiogenesis assessment in invasive breast cancer. Br J Cancer 76: 1046–1054.
Martin, L, Holcombe, C, Green, B, Leinster, SJ & Winstanley, J (1997b). Is a histological section representative of whole tumour vascularity in breast cancer? Br J Cancer 76: 40–43.
Minkowitz, S, Moskowitz, R, Khafif, RA & Alderete, MN (1986). TRU-CUT needle biopsy of the breast. An analysis of its specificity and sensitivity. Cancer 57: 320–323.
Parums, DV, Cordell, JL, Micklem, K, Heryet, AR, Gatter, KC & Mason, DY (1990). JC70: a new monoclonal antibody that detects vascular endothelium associated antigen on routinely processed tissue sections. J Clin Pathol 43: 752–757.
Van Hoef, MEHM, Knox, WF, Dhesi, SS, Howell, A & Schor, AM (1993). Assessment of tumour vascularity as a prognostic factor in lymph node negative breast cancer. Eur J Cancer 29A: 1141–1145.
Vermeulen, PB, Gasparini, G, Fox, SB, Toi, M, Martin, L, McCulloch, P, Pezzella, F, Viale, G, Weidner, N, Harris, AL & Dirix, LY (1996). Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria for evaluation. Eur J Cancer 32A: 2474–2484.
Vermeulen, PB, Libura, M, Libura, J, O’Neill, PJ, van Dam, P, Van Marck, E, Van Oosterom, AT & Dirix, LY (1997). Influence of investigator experience and microscopic field size on microvessel density in node-negative breast carcinoma. Br Cancer Res Treat 42: 165–172.
Weidner, N, Semple, JP, Welch, WR & Folkman, J (1991). Tumor angiogenesis and metastasis – correlation in invasive breast carcinoma. N Engl J Med 324: 1–8.
Weidner, N, Folkman, J, Pozza, F, Bevilacqua, P, Allred, EN, Moore, DH, Meli, S & Gasparini, G (1992). Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84: 1875–1887.
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Marson, L., Kurian, K., Miller, W. et al. Reproducibility of microvessel counts in breast cancer specimens. Br J Cancer 81, 1088–1093 (1999). https://doi.org/10.1038/sj.bjc.6690811
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690811