Breast Cancer

, Volume 8, Issue 2, pp 138–145 | Cite as

Quantitative morphometric analysis of fine needle aspirates of breast carcinoma

  • Masato Suzuki
  • Masaki Oshida
  • Takeshi Nagashima
  • Hideyuki Hashimoto
  • Hiroshi Yagata
  • Nobuyuki Nakajima
Original Article
Received:
Accepted:

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.

Key words

Breast carcinoma Fine needle aspiration Morphometry Quantitative analysis Chemosensitivity 

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

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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1).
    Dabbs DJ: Role of nuclear grading of breast carcinomas in fine needle aspiration specimens.Acta Cytol 37:361–366, 1993.PubMedGoogle Scholar
  2. 2).
    Dabbs DJ, Silverman JF: Prognostic factors from the fine-needle aspirate: breast carcinoma nuclear grade.Diagn Cytopathol 10:203–208, 1994.PubMedCrossRefGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedGoogle Scholar
  7. 7).
    Hunt CM, Ellis IO, Elston CW,et al: Cytological grad- ing of breast carcinoma--a feasible proposition?.Cytopathology 1:287–295, 1990.PubMedCrossRefGoogle Scholar
  8. 8).
    Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer.Br J Cancer 11:359–377, 1957.PubMedGoogle Scholar
  9. 9).
    Black MM, Barclay TH, Hankey BF: Prognosis in breast cancer utilizing histologic characteristics of the primary tumor.Cancer 36:2048–2055, 1975.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 16).
    Zoppi JA, Pellicer EM, Sundblad AS: Cytohistologic correlation of nuclear grade in breast carcinoma.Acta Cytol 41:701–704, 1997.PubMedGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.PubMedGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. 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.CrossRefGoogle Scholar
  29. 29).
    Martin HE, Ellis EB: Biopsy of needle puncture and aspiration.Ann Surg 92:169–181, 1930.PubMedCrossRefGoogle Scholar
  30. 30).
    NIH Consensus Development Conference statement on the treatment of early-stage breast cancer.Oncology 5:120–124, 1991.Google Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.Google Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 34).
    Dalton LW, Page DL, Dupont WD: Histologic grading of breast carcinoma. A reproducibility study.Cancer 73:2765–2770, 1994.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2001

Authors and Affiliations

  • Masato Suzuki
    • 1
  • Masaki Oshida
    • 1
  • Takeshi Nagashima
    • 1
  • Hideyuki Hashimoto
    • 1
  • Hiroshi Yagata
    • 1
  • Nobuyuki Nakajima
    • 1
  1. 1.The First Department of SurgeryChiba University School of MedicineJapan

Personalised recommendations