Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Spectral morphometric characterization of breast carcinoma cells

British Journal of Cancer volume 79, pages 1613–1619 (1999)Cite this article

This article has been updated

Summary

The spectral morphometric characteristics of standard haematoxylin and eosin breast carcinoma specimens were evaluated by light microscopy combined with a spectral imaging system. Light intensity at each wavelength in the range of 450–800 nm was recorded for 104 pixels from each field and represented as transmitted light spectra. A library of six characteristic spectra served to scan the cells and reconstruct new images depicting the nuclear area occupied by each spectrum. Fifteen cases of infiltrating ductal carcinoma and six cases of lobular carcinoma were examined; nine of the infiltrating ductal carcinoma and three of the lobular carcinoma showed an in situ component. The spectral morphometric analysis revealed a correlation between specific patterns of spectra and different groups of breast carcinoma cells. The most consistent result was that lobular carcinoma cells of in situ and infiltrating components from all patients showed a similar spectral pattern, whereas ductal carcinoma cells displayed spectral variety. Comparison of the in situ and the infiltrating ductal solid, cribriform and comedo carcinoma cells from the same patient revealed a strong similarity of the spectral elements and their relative distribution in the nucleus. The spectrum designated as number 5 in the library incorporated more than 40% of the nuclear area in 74.08% of the infiltrating lobular cells and in 13.64% of the infiltrating ductal carcinoma cells (P < 0.001). Spectrum number 2 appeared in all infiltrating ductal cells examined and in none of the lobular cells. These results indicate that spectrum number 5 is related to infiltrating lobular carcinoma, whereas spectrum number 2 is characteristic for infiltrating ductal carcinoma cells. Spectral similarity mapping of central necrotic regions of comedo type in situ carcinoma revealed nuclear fragmentation into defined segments composed of highly condensed chromatin. We conclude that the spectral morphometric features found for lobular and ductal cell populations may serve future automated histological diagnostics.

Download 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

  • Azzopardi, J. G., Chepick, O. F., Hartmann, W. H., Jafarey, N. A., Lombart-Bosch, A. & Ozello, L. (1982). The World Health Organization histological typing of breast tumors 2nd ed. Am J Clin Pathol 78: 806–816.

    Article  Google Scholar 

  • Baak, J. P. A. & Oort, J. (1983). A manual of morphometry. In, Diagnostic Pathology, Baak JP and Oort J (eds). Springer-Verlag: Berlin

    Google Scholar 

  • Cornelisse, C. J., de Konig, H. R., Moolenaar AJ van de Velde, C. J. & Ploem, J. S. (1984). Image and flow cytometric analysis of DNA content in breast cancer; relation to estrogen receptor content and lymph node involvement. Anal Quant Cytol Histol 4: 9–18.

    Google Scholar 

  • Dawson, A. E., Austin, R. E. & Weinberg, D. S. (1991). Nuclear grading of breast carcinoma by image analysis. Classification by multivariate and neural network analysis. Am J Clin Pathol 95: S29–S37.

    CAS  PubMed  Google Scholar 

  • DiConstanzo, D., Rosen, P. P., Gareen, I., Franklin, S. & Lesser, M. (1990). Prognosis in infiltrating lobular carcinoma: an analysis of “classical” and variant tumors. Am J Surg Pathol 14: 12–23.

    Article  Google Scholar 

  • Ellis, I. O., Galea, M., Broughton, N., Locker, A., Blaney, R. W. & Elston, C. (1992). Pathological prognostic factors in breast cancer: II Histological type; relationship with survival in a large study with long term follow-up. Histopathology 20: 479–489.

    CAS  Article  Google Scholar 

  • Eskelinen, M., Lipponen, P., Papinaho, S., Aaltomaa, S., Kosma, V. m. & Klemi, P. (1996). DNA flow cytometry, nuclear morphometry, mitotic indices and steroid receptors as independent prognostic factors in female breast cancer. Int J Cancer 51: 555–561.

    Article  Google Scholar 

  • Farmer, E. R., Gonin, R. & Hanna, M. P. (1996). Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol 27: 528–531.

    CAS  Article  Google Scholar 

  • Fisher, E. R., Gregorio, R. M. & Fisher, B. (1975). The pathology of invasive breast cancer. A syllabus derived from findings of the national surgical adjuvant breast project (protocol no. 4). Cancer 36: 1–85.

    CAS  Article  Google Scholar 

  • Galbraith, W., Marshall, P. N. & Bacus, J. W. (1980). Microspectrophotometric studies of Romanowsky stained blood cells. I. Subtraction analysis of a standardized procedure. J Microsc 119: 313–330.

    CAS  Article  Google Scholar 

  • Gallager, H. S. & Hutter, R. V. P. (1978). Pathology and pathogenesis of breast cancer. In The Breast. Gallager HS, Leis HP, Snydcran RK, Urban IA (eds), p. 49. CV Mosby: St Louis

    Google Scholar 

  • Garini, Y., Katzir, N., Cabib, D., Buckwald, R. A., Soenksen, D. & Malik, Z. (1996a). Spectral Bio-Imaging. In Fluorescence Imaging Spectroscopy and Microscopy. Wang XF, Herman B (eds), p. 87. Wiley and Sons: New York

    Google Scholar 

  • Garini, Y., MacvM, du Manoir, S., Buckwald, R. A., Lavi, M., Katzir, N., Wine, D., Bar-Am, I., Schrock, E., Cabib, D. & Ried, T. (1996b). Spectral karyotyping. Bioimaging 4: 64–72.

    Article  Google Scholar 

  • Gilchrist, K. W., Kalish, L., Gould, V. E., Hirschl, S., Imbriglia, J. E., Levy, W. M., Patchefsky, A. S., Penner, D. W., Pickren, J., Roth, J. A., Schinella, R. A., Schwart, I. S. & Wheeler, J. E. (1985). Inter-observer reproducibility of histopathological features in stage II breast cancer: an ECOG study. Breast Cancer Res Treat 5: 3–10.

    CAS  Article  Google Scholar 

  • Gundersen, H. S. G. & Jensen, E. B. (1987). The efficiency of systematic sampling in stereology and prediction. J Microsc 147: 229–234.

    CAS  Article  Google Scholar 

  • Hartmann, W. H., Ozzello, L., Sobin, L. H. & Stalsberg, H. (1981). Histologic Typing of Breast Tumors. World Health Organization: Geneva

    Google Scholar 

  • Heppner, G. H. (1984). Tumor heterogeneity. Cancer Res 44: 2259–2265.

    CAS  PubMed  Google Scholar 

  • Komitowski, D. D. & Janson, C. P. (1990). Quantitive features of chromatin structure in the prognosis of breast cancer. Cancer 65: 2725–2730.

    CAS  Article  Google Scholar 

  • Komitowski, D. D., Hart, M. M. & Janson, C. P. (1993). Chromatin organization and breast cancer prognosis; two dimensional and three dimensional image analysis. Cancer 72: 1239–1246.

    CAS  Article  Google Scholar 

  • Ladekarl, M. & Sorensen, F. B. (1993). Quantitive histopathological variables in in situ and invasive ductal carcinoma of the breast. APMIS 101: 895–903.

    CAS  Article  Google Scholar 

  • Ladekarl, M. (1995). Quantitative histopathology in ductal carcinoma of the breast. Prognostic value of mean nuclear size and mitotic counts. Cancer 75: 2114–2122.

    CAS  Article  Google Scholar 

  • Lagios, M. D. (1990). Duct carcinoma in situ pathology and treatment. Surg Clin North Am 70: 853–871.

    CAS  Article  Google Scholar 

  • Lennington, W. J., Jensen, R. A., Dalton, L. W. & Page, D. L. (1994). Ductal carcinoma in situ of the breast. Heterogeneity of individual lesions. Cancer 73: 118–124.

    CAS  Article  Google Scholar 

  • Malik, Z., Dishi, M. & Garini, Y. (1996a). Fourier transform multipixel spectroscopy and spectral imaging of protoporphyrin in single melanoma cells. Photochem Photobiol 63: 608–614.

    CAS  Article  Google Scholar 

  • Malik, Z., Cabib, D., Buckwald, R. A., Talmi, Y., Garini, Y. & Lipson, S. G. (1996b). Fourier transform multipixel spectroscopy for quantitative cytology. J Microsc 182: 133–140.

    CAS  Article  Google Scholar 

  • Malik, Z., Amit, I. & Rothmann, C. (1997). Subcellular localization of sulfonated tetraphenyl porphines in colon carcinoma cells by spectrally resolved imaging. J Photochem Photobiol 65: 389–396.

    CAS  Article  Google Scholar 

  • Page, D. L. & Anderson, T. G. (1987). Diagnostic Histopathology of the Breast, Churchill Livingstone: Edinburgh

    Google Scholar 

  • Pienta, K. J. & Coffey, D. S. (1991). Correlation of nuclear morphometry with progression of breast cancer. Cancer 68: 2012–2015.

    CAS  Article  Google Scholar 

  • Rothmann, C., Cohen, A. M. & Malik, Z. (1997). Chromatin condensation in erythropoiesis resolved by multi-pixel spectral imaging: differentiation versus apoptosis. J Histochem Cytochem 45: 1097–1108.

    CAS  Article  Google Scholar 

  • Scarff, R. W. & Torloni, H. (1968). Histologic typing of breast tumors. In International Classification of Tumors, Vol. 2, Scarff RW and Torloni H (eds), p. 19. World Health Organization: Geneva

    Google Scholar 

  • Schrock, E., du Manoir, S., Veldman, T., Schoell, B., Wienberg, J., Ferguson-Smith, M. A., Ning, Y., Ledbetter, D. H., Bar-Am, I., Soenksen, D., Garini, Y. & Ried, T. (1996). Multicolor spectral karyotyping of human chromosomes. Science 273: 494–497.

    CAS  Article  Google Scholar 

  • Smith, R. & Crocker, J. (1988). Evaluation of nucleolar organizer region associated proteins in breast malignancy. Histopathology 12: 113–125.

    CAS  Article  Google Scholar 

  • Spina, D., Disanto, A., Luzi, P., Tosi, P., Gallorini, M., Mouthon, A. M., Kraft, R. & Cottier, H. (1992). Novel, contrast gradient-oriented, automated chromatin texture analysis. Feasibility study on nuclei from benign and malignant breast epithelial cell lines in fine needle aspirates. Virchows Arch B Cell Pathol 62: 119–124.

    CAS  Article  Google Scholar 

  • Stenkvist, B., Westman-Naeser, S., Vegelius, J., Holmquist, J., Nordin, B., Bengtsson, E. & Eriksson, O. (1978). Computerized nuclear morphology as an objective method for characterizing human cancer cell populations. Cancer Res 38: 4688–4977.

    CAS  PubMed  Google Scholar 

  • Stoll, B. A. (1986). Components of a prognostic index. In Breast Cancer Treatment and Prognosis, Stoll BA (ed), p. 115. Blackwell Scientific Publications: London

    Google Scholar 

  • Toikkanen, S. & Jensuu, H. (1990). Prognostic factors and long-term survival in breast cancer in a defined urban population. APMIS 98: 1005–1014.

    CAS  Article  Google Scholar 

  • du Toit, R. S., Locker, A. P., Ellis, I. O., Elston, C. W., Nicholson, R. I. & Robertson, J. F. R. (1991). An evaluation of differences in prognosis, recurrence patterns and receptor status between invasive lobular and other invasive carcinomas of the breast. Eur J Surg Oncol 17: 251–257.

    CAS  PubMed  Google Scholar 

  • Veldman, T., Vignon, C., Schrock, E., Rowley, J. D. & Ried, T. (1997). Hidden chromosome abnormalities in haematological malignancies detected by multicolor spectral karyotyping. Nature Genet 15: 406–410.

    CAS  Article  Google Scholar 

  • Wells, W. A., Rainer, R. O. & Memoli, V. A. (1992). Basic principles of image processing. Am J Clin Pathol 98: 493–501.

    CAS  Article  Google Scholar 

  • Yu, G. H., Sneige, N., Kidd, L. D., Johnston, & Katz, R. L. (1995). Image analysis derived morphometric differences in fine needle aspirates of ductal and lobular breast carcinoma. Anal Quant Cytol Histol 17: 88–92.

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Pathology Department, Sheba Medical Center, Tel-Hashomer, 52621, Israel

    I Barshack & J Kopolovic

  2. Life Sciences Department, Microscopy Unit, Bar-Ilan University, Ramat-Gan, 52900, Israel

    Z Malik & C Rothmann

Authors
  1. I Barshack
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Kopolovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Z Malik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Rothmann
    View author publications

    You can also search for this author in PubMed Google Scholar

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/

Reprints and Permissions

About this article

Cite this article

Barshack, I., Kopolovic, J., Malik, Z. et al. Spectral morphometric characterization of breast carcinoma cells. Br J Cancer 79, 1613–1619 (1999). https://doi.org/10.1038/sj.bjc.6690257

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bjc.6690257

Keywords

  • spectral morphometry
  • spectral similarity mapping
  • in situ and infiltrating ductal and lobular breast carcinoma

Further reading

Search

Advanced search

Quick links