Abstract
In the National Surgical Adjuvant Study for Breast Cancer (NSAS‐BC), node‐negative breast cancers were divided into higher‐ and lower‐risk groups according to the histopathological nuclear grade given at individual collaborating hospitals, and the higher‐risk group was entered into a randomized protocol of adjuvant therapy. Because the nuclear grade was the composite of nuclear atypia and mitotic counts, maintenance of interobserver agreement in mitotic counts was indispensable for the success of the protocol study. Fourteen pathologists participating in the protocol judged whether or not 20 photomicrographs suspected of showing mitotic cancer‐cell figures truly showed mitoses. After standardizing the counting method, these pathologists counted the number of mitotic figures per 10 high‐power fields of hematoxylin‐eosin‐stained main‐tissue sections of 20 tumors. Areas where mitotic counts were considered to be the most frequent by each pathologist were compared for these tumors. For the judgment of whether the photomicrograph indicated mitosis, the level of interobserver agreement was moderate (k=0.569). In the observations of 20 tumors, interobserver agreement level of mitotic counts was moderate (k=0.506), that of nuclear atypia scoring was fair (k=0.265), and that of nuclear grading was substantial (k=0.633). The counted area was almost the same among the observers in 9 tumors, split into two areas in 6, and dispersed in 5. Concordance in judgment was achieved in 7 of the first 9 and in all of the third 5, but only in one of the second 6. The cause of discordance was mostly derived from tumor heterogeneity and the difference in the site where mitoses were counted. Interobserver agreement level was considered to be satisfactory, and it was expected that the case entry would be performed appropriately in the protocol study. The selection of the counting area was confirmed to be important for the acquisition of high‐level agreement level in mitotic counts.
Keywords: Breast cancer, Mitotic figures, Interobserver agreement, Protocol study
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REFERENCES
- 1. ) Bloom , H. J. G. and Richardson , W. W.Histological grading and prognosis in breast cancer . Br. J. Cancer , 11 , 359 – 377 ( 1957. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. ) Contesso , G. , Mouriesse , H. , Friedman , S. , Genin , D. , Sarrazin , D. and Rouesse , J.The importance of histologic grade in long‐term prognosis of breast cancer: a study of 1,010 patients, uniformly treated at the Institut Gustave‐Roussy . J. Clin. Oncol. , 5 , 1378 – 1386 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Elston , C. W.Grading of invasive carcinoma of the breast . In“Diagnostic Histopathology of the Breast ,” ed. Page D. L. and Anderson T. V. , pp. 300 – 311 ( 1987. ). Churchill Livingstone; , New York . [Google Scholar]
- 4. ) Simpson , J. F. , Dutt , P. L. and Page , D. L.Expression of mitoses per thousand cells and cell density in breast carcinomas: a proposal . Hum. Pathol. , 23 , 608 – 611 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 5. ) van Diest , P. J. , Baak , J. P. A. , Matze‐Cok , P. , Wisse‐Brekelmans , E. C. M. , van Galen , C. M. , Kurver , P. H. J. , Bellot , S. M. , Fijnheer , J. , van Gorp , L. H. M. , Kwee , W. S. , Los , J. , Peterse , J. L. , Ruitenberg , H. M. , Schapers , R. F. M. , Schipper , M. E. I. , Somsen , J. G. , Willig , A. W. P. M. and Ariens , A. T.Reproducibility of mitosis counting in 2,469 breast‐cancer specimens: results from the multicenter morphometric mammary carcinoma project . Hum. Pathol. , 23 , 603 – 607 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Hilsenbeck , S. G. and Allred , D. C.Improved methods of estimating mitotic activity in solid tumors . Hum. Pathol. , 23 , 601 – 602 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Tsuda , H. , Akiyama , F. , Kurosumi , M. , Sakamoto , G. and Watanabe , T . for the NSAS‐BC pathology section. Establishment of histological criteria for high‐risk node‐negative breast carcinoma in a randomized clinical trial of adjuvant therapy . Jpn. J. Clin. Oncol. , 28 , 486 – 491 ( 1998. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Tsuda , H. , Akiyama , F. , Kurosumi , M. , Sakamoto , G. , Watanabe , T.and NSAS‐BC collaborating pathologists. The efficacy and limitations of repeated slide conferences for improving interobserver agreement when judging nuclear atypia of breast cancer . Jpn. J. Clin. Oncol. , 29 , 68 – 73 ( 1999. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Tsuda , H. , Akiyama , F. , Kurosumi , M. , Sakamoto , G. and Watanabe , T . for the NSAS‐BC pathology section. Monitoring of interobserver agreement in nuclear atypia scoring of node‐negative breast carcinomas judged at individual collaborating hospitals in the National Surgical Adjuvant Study of Breast Cancer (NSAS‐BC) protocol . Jpn. J. Clin. Oncol. , 29 , 413 – 420 ( 1999. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Gilbert , S. F.“Developmental Biology ,” 3rd Ed. , pp. 3 – 32 ( 1991. ). Sinauer Associates; , Sunderland . [Google Scholar]
- 11. ) Fleiss , J. L.Measuring nominal scale agreement among many raters . Psychol. Bull. , 76 , 378 – 382 ( 1971. ). [Google Scholar]
- 12. ) Light , R. J.Measures of response agreement for qualitative data: some generalizations and alterations . Psychol. Bull. , 76 , 365 – 377 ( 1971. ). [Google Scholar]
- 13. ) Fleiss , J. L.“Statistical Methods for Rates and Proportions ,” pp. 212 – 236 ( 1981. ). John Wiley & Sons; , New York . [Google Scholar]
- 14. ) Landis , J. R. and Koch , G. G.The measurement of observer agreement for categorical data . Biometrics , 33 , 159 – 174 ( 1977. ). [PubMed] [Google Scholar]
- 15. ) Græm , N. and Helwig‐Larsen , K.Mitotic activity and delay in fixation of tumour tissue . Acta Pathol. Microbiol. Scand. A , 87 , 375 – 378 ( 1979. ). [PubMed] [Google Scholar]
- 16. ) Donhuijsen , K. , Schmidt , U. , Hirche , H. , van Beuningen , D. and Budach , V.Changes in mitotic rate and cell cycle fractions caused by delayed fixation . Hum. Pathol. , 21 , 709 – 714 ( 1990. ). [DOI] [PubMed] [Google Scholar]