Skip to main content
Log in

Quantitative morphometric analysis of fine needle aspirates of breast carcinoma

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Background

Reports of morphometric analysis using computerized digitized images of fine needle aspirates of breast cancer are rare. We aimed to evaluate whether quantitative morphometric estima-tions of cytological nuclear features could be used for preoperative prediction of the risk of recurrence as well as chemosensitivity.

Methods

Seventy consecutive breast cancer patients were treated with preoperative chemotherapy (Doxifluridine 800 mg/body/day, orally) for 4 weeks and subsequently they underwent surgery. Using Papanicolaou-stained cytological materials, computerized morphometric analyses were performed. Mean nuclear area (NA) was measured and the coefficient of variation of NA (NACV) was calculated as the quantitative parameter of nuclear atypism. NA and NACV were compared with prognostic factors (tumor size, histological grade, hormone receptor status, nodal status, and ploidy status), and with the response to the chemotherapy.

Results

NA and NACV were significantly associated with hormone receptor status and ploidy status (p<0.05). NACV correlated with histological grade (p<0.05). Neither NA nor NACV were associated with tumor size and nodal status. Patients with high NACV (>35%) had lower rates of disease-free survival (p<0.05) than those with low NACV (≦35%). Responders to preoperative chemotherapy had statistically larger NA, higher NACV and higher S-phase fraction at the time of diagnosis compared with non-responders (p<0.001,p<0.0005, andp<0.05 respectively).

Conclusions

Morphometric analysis of preoperative fine needle aspirates reflects important clinical information, such as the risk of recurrence, and particularly, chemosensitivity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

FNAC:

Fine needle aspiration cytology

FCM:

Flow cytometry

NA:

Nuclear area

NACV:

Coefficient of variation of nuclear area

SD:

Standard deviation

Dl:

DNA index

SPF:

S-phase fraction

ER:

Estrogen receptor

PgR:

Progesterone receptor

CNB:

Core needle biopsy

References

  1. Dabbs DJ: Role of nuclear grading of breast carcinomas in fine needle aspiration specimens.Acta Cytol 37:361–366, 1993.

    PubMed  CAS  Google Scholar 

  2. Dabbs DJ, Silverman JF: Prognostic factors from the fine-needle aspirate: breast carcinoma nuclear grade.Diagn Cytopathol 10:203–208, 1994.

    Article  PubMed  CAS  Google Scholar 

  3. Layfield LJ, Robert ME, Cramer H,et al: Aspiration biopsy smear pattern as a predictor of biologic behav- ior in adenocarcinoma of the breast.Acta Cytol 36:208–214, 1992.

    PubMed  CAS  Google Scholar 

  4. Briffod M, Le Doussal V, Spyratos F: Cytologic nuclear grading of fine needle cytopunctures of breast carcinoma. Comparison with histologic nuclear grading and image cytometric data.Anal Quant Cytol Histol 19:114–122, 1997.

    PubMed  CAS  Google Scholar 

  5. Cajulis RS, Hessel RG, Hwang S,et al: Simplified nuclear grading of fine-needle aspirates of breast car- cinoma: concordance with corresponding histologic nuclear grading and flow cytometric data.Diagn Cytopathol 11:124–130, 1994.

    Article  PubMed  CAS  Google Scholar 

  6. Cajulis RS, Hessel RG, Frias-Hidvegi D,et al: Cytologic grading of fine needle aspirates of breast carcinoma by private practice pathologists.Acta Cytol 41:313–320, 1997.

    PubMed  CAS  Google Scholar 

  7. Hunt CM, Ellis IO, Elston CW,et al: Cytological grad- ing of breast carcinoma--a feasible proposition?.Cytopathology 1:287–295, 1990.

    Article  PubMed  CAS  Google Scholar 

  8. Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer.Br J Cancer 11:359–377, 1957.

    PubMed  CAS  Google Scholar 

  9. Black MM, Barclay TH, Hankey BF: Prognosis in breast cancer utilizing histologic characteristics of the primary tumor.Cancer 36:2048–2055, 1975.

    Article  PubMed  CAS  Google Scholar 

  10. Fisher B, Fisher ER, Redmond C,et al: Tumor nuclear grade, estrogen receptor, and progesterone receptor: Their value alone or in combination as indi- cators of outcome following adjuvant therapy for breast cancer.Breast Cancer Res Treat 7:147–160, 1986.

    Article  PubMed  CAS  Google Scholar 

  11. Le Doussal V, Tubiana-Hulin M, Friedman S,et al: Prognostic value of histologic grade nuclear components of Scarff-Bloom- Richardson (SBR). An improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas.Cancer 64:1914–1921, 1989.

    Article  PubMed  CAS  Google Scholar 

  12. Stierer M, Rosen H, Weber R: Nuclear pleomor- phism, a strong prognostic factor in axillary node- negative small invasive breast cancer.Breast Cancer Res Treat 20:109–116, 1992.

    Article  PubMed  CAS  Google Scholar 

  13. Davey DD, Banks ER, Jennings D,et al: Comparison of nuclear grade and DNA cytometry in breast carci- noma aspirates to histologic grade in excised can- cers.Am J Clin Pathol 99:708–713, 1993.

    PubMed  CAS  Google Scholar 

  14. Ducatman BS, Emery ST, Wang HH: Correlation of histologic grade of breast carcinoma with cytologic features on fine-needle aspiration of the breast.Mod Pathol 6:539–543, 1993.

    PubMed  CAS  Google Scholar 

  15. Robinson IA, McKee G, Nicholson A,et al: Prognostic value of cytological grading of fine-needle aspi- rates from breast carcinomas.Lancet 343:947–949, 1994.

    Article  PubMed  CAS  Google Scholar 

  16. Zoppi JA, Pellicer EM, Sundblad AS: Cytohistologic correlation of nuclear grade in breast carcinoma.Acta Cytol 41:701–704, 1997.

    PubMed  CAS  Google Scholar 

  17. Moroz K, Lipscomb J, Vial LJ,et al: Cytologic nuclear grade of malignant breast aspirates as a predictor of histologic grade. Light microscopy and image analysis characteristics.Acta Cytol 41:1107–1111, 1997.

    PubMed  CAS  Google Scholar 

  18. Pinder SE, Murray S, Ellis IO,et al: The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy.Cancer 83:1529–1539, 1998.

    Article  PubMed  CAS  Google Scholar 

  19. Fisher ER, Anderson S, Redmond C,et al: Pathologic findings from the National Surgical Adjuvant Breast Project protocol B-06. 10-year pathologic and clinical prognostic discriminants.Cancer 71:2507–2514, 1993.

    Article  PubMed  CAS  Google Scholar 

  20. Mouriquand J, Gozlan-Fior M, Villemain D,et al: Value of cytoprognostic classification in breast carci- nomas.J Clin Pathol 39:489–496, 1986.

    Article  PubMed  CAS  Google Scholar 

  21. Thomas JS, Mallon EA, George WD: Semiquantitative analyses of fine needle aspirates from benign and malignant breast lesions.J Clin Pathol 42:28–34, 1989.

    Article  PubMed  CAS  Google Scholar 

  22. Stenkvist B, Westman-Naeser S, Holmquist J,et al: Computerized nuclear morphometry as an objective method for characterizing human cancer cell popula- tions.Cancer Res 38:4688–4697, 1978.

    PubMed  CAS  Google Scholar 

  23. Wolberg WH, Street WN, Heisey DM,et al: Computerized breast cancer diagnosis and prognosis from fine-needle aspirates.Archives of Surgery 130:511–516, 1995.

    PubMed  CAS  Google Scholar 

  24. Kimijima I, Watanabe T, Abe R: Prognostic value of nuclear grading by image cytometry for node nega- tive breast cancer patients.Anticancer Res 16:3949–3954, 1996.

    PubMed  CAS  Google Scholar 

  25. Cook AF, Holman MJ, Kramer MJ,et al: Fluorinated pyrimidine nucleosides. 3. Synthesis and antitumor activity of a series of 5’-deoxy-5-fluoropyrimidine nucleosides.J Med Chem 22:1330–1335, 1979.

    Article  PubMed  CAS  Google Scholar 

  26. Miwa M, Ura M, Nishida M,et al: Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue.Eur J Cancer 34:1274–1281, 1998.

    Article  PubMed  CAS  Google Scholar 

  27. Ishikawa T, Sekiguchi F, Fukase Y,et al: Positive cor- relation between the efficacy of capecitabine and dox- ifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts.Cancer Res 58:685–690, 1998.

    PubMed  CAS  Google Scholar 

  28. Committee for Production of Histopathological Criteria, Japanese Breast Cancer Society: Histopathologi- cal criteria for assessment of therapeutic response in breast cancer.Breast Cancer 8:1–2, 2001.

    Article  Google Scholar 

  29. Martin HE, Ellis EB: Biopsy of needle puncture and aspiration.Ann Surg 92:169–181, 1930.

    Article  PubMed  CAS  Google Scholar 

  30. NIH Consensus Development Conference statement on the treatment of early-stage breast cancer.Oncology 5:120–124, 1991.

    Google Scholar 

  31. Stenkvist B, Westman-Naeser S, Vegelius J,et al: Analysis of reproducibility of subjective grading sys- tems for breast carcinoma.J Clin Pathol 32:979–985, 1979.

    Article  PubMed  CAS  Google Scholar 

  32. Baak JP, Persijn JP: In search for the best qualitative microscopical or morphometrical predictor of oestro- gen receptor in breast cancer.Pathology, Research & Practice 178:307–314, 1984.

    CAS  Google Scholar 

  33. Baak JP, Van Dop H, Kurver PH,et al: The value of morphometry to classic prognosticators in breast cancer.Cancer 56:374–382, 1985.

    Article  PubMed  CAS  Google Scholar 

  34. Dalton LW, Page DL, Dupont WD: Histologic grading of breast carcinoma. A reproducibility study.Cancer 73:2765–2770, 1994.

    Article  PubMed  CAS  Google Scholar 

  35. Robbins P, Pinder S, de Klerk N,et al: Histological grading of breast carcinomas: a study of interobserv- er agreement.Hum Pathol 26:873–879, 1995.

    Article  PubMed  CAS  Google Scholar 

  36. Balslev I, Axelsson CK, Zedeler K,et al: The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG).Breast Cancer Res Treat 32:281–290, 1994.

    Article  PubMed  CAS  Google Scholar 

  37. Galea MH, Blarney RW, Elston CE,et al: The Notting- ham Prognostic Index in primary breast cancer.Breast Cancer Res Treat 22:207–219, 1992.

    Article  PubMed  CAS  Google Scholar 

  38. Miyauchi M: Objective evaluation of nuclear grade in preoperative aspiration materials from breast can- cers-special reference to the relationship of coeffi- ciency variant of nuclear area with pathological prog- nostic features.Nippon Geka Gakkai Zasshi 92:1642–1649, 1991.

    PubMed  CAS  Google Scholar 

  39. Briffod M, Spyratos F, Tubiana-Hulin M,et al: Sequential cytopunctures during preoperative chemotherapy for primary breast carcinoma. Cyto- morphologic changes, initial tumor ploidy, and tumor regression.Cancer 63:631–637, 1989.

    Article  PubMed  CAS  Google Scholar 

  40. Levack PA, Mullen P, Anderson TJ,et al: DNA analysis of breast tumor fine needle aspirates using flow cytometry.Br J Cancer 56:643–646, 1987.

    PubMed  CAS  Google Scholar 

  41. Briffod M, Spyratos F, Hacene K,et al: Evaluation of breast carcinoma chemosensitivity by flow cytometric DNA analysis and computer assisted image analysis.Cytometry 13:250–258, 1992.

    Article  PubMed  CAS  Google Scholar 

  42. Sarker S, Spigelman A, Walker M,et al: Nuclear DNA content of fine needle aspirates of invasive ductal carcinomas of the breast.Anal Cell Pathol 13:1–8, 1997.

    PubMed  CAS  Google Scholar 

  43. Ballo MS, Sneige N: Can core needle biopsy replace fine-needle aspiration cytology in the diagnosis of pal- pable breast carcinoma.Cancer 78:773–737, 1996.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Suzuki, M., Oshida, M., Nagashima, T. et al. Quantitative morphometric analysis of fine needle aspirates of breast carcinoma. Breast Cancer 8, 138–145 (2001). https://doi.org/10.1007/BF02967493

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02967493

Key words

Navigation