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Mitosis Counting

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Assessment of Cell Proliferation in Clinical Practice

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Abstract

It is a truism to say that the main (nay, only) method of assessing cell proliferation which has enjoyed any routine popularity has been the assessment of mitotic activity. This is obviously because nothing special has to be done to the tissues (indeed routine sections are usually used). However, instead of approaching such measurements on an appropriate basis, i.e. achieving measurements of accuracy and known precision, most workers have relied on easy, non-critical, rule-of-thumb assessments. Such an approach is, in our opinion, a perfect recipe for disaster. In this chapter we review the several methods of assessing mitotic activity, the purported role of these measurements in prognosis, and reflect on the vagaries of these measurements.

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References

  • Aherne WA, Camplejohn RS and Wright NA (1977a) An introduction to cell population kinetics. Edward Arnold, London

    Google Scholar 

  • Aherne WA, Al-Wiswazy M, Ford D and Kellerer AM (1977b) Assessment of inherent fluctuations of mitotic and labelling indices of human tumours. Br J Cancer 36:577–591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Akerman M, Brandt L, Johnson A and Olsson H (1987) Mitotic activity in non-Hodgkin’s lymphoma. Relation to the Kiel classification and to prognosis. Br J Cancer 55:219–223

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Appelman HD and Helwig EB (1976) Gastric epithelioid leiomyoma and leiomyosarcoma (leiomyoblastoma). Cancer 38:709–728

    Article  Google Scholar 

  • Appelman HD and Helwig EB (1977) Cellular leiomyomas of the stomach in 49 patients. Arch Pathol Lab Med 101:373–377

    CAS  PubMed  Google Scholar 

  • Baak JPA (1990) Mitosis counting in tumors. Hum Pathol 21:683–685

    Article  CAS  PubMed  Google Scholar 

  • Baak JP, Lindeman J, Overdiep SH and Langley FA (1982) Disagreement of histopathological diagnoses of different pathologists in ovarian tumors - with some theoretical considerations. Eur J Obstet Gynecol Reprod Biol 13:51–55

    Article  CAS  PubMed  Google Scholar 

  • Baak JP, Langley FA, Talerman A and Delemarre JF (1986) Interpathologist and intrapathologist disagreement in ovarian tumor grading and typing. Anal Quant Cytol Histol 8:354–357

    CAS  PubMed  Google Scholar 

  • Baak JP, Wisse Brekelmans EC, Uyterlinde AM and Schipper NW (1987) Evaluation of the prognostic value of morphometric features and cellular DNA content in FIGO I ovarian cancer patients. Anal Quant Histol Cytol 9:287–290

    CAS  Google Scholar 

  • Baak JPA, Schipper NW, Wisse-Brekelmans ECM et al. (1988) The prognostic value of morphometrical features and cellular DNA content in cisplatin treated late ovarian cancer patients. Br J Cancer 57:503–508

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Baak JPA, van Diest PJ and Ariens ATH, et al. The multicenter morphometric mammary carcinoma project (1989) A nationwide prospective study on reproducibility and prognostic power of routine quantitive assessments in the Netherlands. Pathol Res Pract 185:664–670

    Article  CAS  PubMed  Google Scholar 

  • Bell DA, Weinstock MA and Scully RE (1988) Peritoneal implants of ovarian serous borderline tumors. Histologic features and prognosis. Cancer 62:2212–2222

    Article  CAS  PubMed  Google Scholar 

  • Bennett MH, Farrer-Brown G, Henry K and Jelliffe JM (1974) Classification of non Hodgkins lymphoma. Lancet ii:405–406

    Article  Google Scholar 

  • Bucsema J, Carpenter SE, Rosenshein NB and Woodruff JD (1986) Epithelioid leiomyosarcoma of the uterus. Cancer 57:1192–1196

    Article  Google Scholar 

  • Burns B, Curry RH and Bell MEA (1979) Morphological features of prognostic significance in uterine smooth muscle tumors: a review of eighty-four cases. Am J Obstet Gynecol 135:109–114

    CAS  PubMed  Google Scholar 

  • Busch CH and Vasko J (1988) Differential staining of mitoses in tissue sections and cultured cells by a modified methenamine silver method. Lab Invest 59:876–878

    CAS  PubMed  Google Scholar 

  • Camplejohn RS, Bone G and Aherne WA (1973) Cell proliferation in rectal carcinoma and rectal mucosa. A stathmokinetic study. Eur J Cancer 9:577–581

    Article  CAS  PubMed  Google Scholar 

  • Christopherson WM, Williamson EO and Gray LA (1972) Leiomyosarcoma of the uterus. Cancer 29:1512–1517

    Article  CAS  PubMed  Google Scholar 

  • De Potter CR, Praet MM, Slavin RE, Verbeeck P and Roels HJ (1987) Feulgen DNA content and mitotic activity in proliferative breast disease. A comparison with ductal carcinoma in situ. Histopathology 11:1307–1319

    Article  PubMed  Google Scholar 

  • De Fusco PA, Gaffey TA, Malkasian GD, Long HJ and Cha SS (1989) Endometrial stromal sarcoma: review of Mayo Clinic experience 1945–1980. Gynecol Oncol 35:8–14

    Article  PubMed  Google Scholar 

  • Donhuijsen K (1986) Mitosis counts. Reproducibility and significance in grading of malignancy. Hum Pathol 17:1122–1125

    Article  CAS  PubMed  Google Scholar 

  • Donhuijsen K (1987) Mitoses in non Hodgkin’s lymphoma. Frequency and prognostic relevance. Pathol Res Pract 182:352–357

    Article  CAS  PubMed  Google Scholar 

  • Donhuijsen K, Schmidt U, Hirche H, van Beunningen D and Budach V (1990) Changes in mitotic rate and cell cycle fractions caused by delayed fixation. Hum Pathol 21:709–714

    Article  CAS  PubMed  Google Scholar 

  • Duffill M, Wright N and Shuster S (1976) The cell proliferation kinetics of psoriasis examined by three in vivo techniques. Br J Dermatol 94:355–362

    Article  CAS  PubMed  Google Scholar 

  • Eckstein RP, Paradinas RF and Bagshawe KD (1982) Placental site trophoblastic tumor: a study of four cases requiring hysterectomy including one fatal case. Histopathology 6:211–226

    Article  CAS  PubMed  Google Scholar 

  • Eckstein RP, Russell P, Friedlander ML, Tattersall MHN and Bradfield A (1985) Metastasising placental site trophoblastic tumor: a case study. Hum Pathol 16:632–636

    Article  CAS  PubMed  Google Scholar 

  • Edwards JL and Donalson JT (1964) The time of fixation and the mitotic index. Am J Clin Pathol 41:158–162

    CAS  PubMed  Google Scholar 

  • Ellis PSJ and Whitehead R (1981) Mitosis counting - a need for reappraisal. Hum Pathol 12:3–4

    Article  CAS  PubMed  Google Scholar 

  • Evans HL (1982) Endometrial stromal sarcoma and poorly differentiated endometrial sarcoma. Cancer 50:2170–2182

    Article  CAS  PubMed  Google Scholar 

  • Evans HL (1985) Spiooth muscle tumors of the gastrointestinal tract. A study of 56 cases followed for a minimum of 10 years. Cancer 56:2242–2250

    Article  CAS  PubMed  Google Scholar 

  • Evans HL, Butler J J and Youness EL (1978) Malignant lymphoma, small lymphocytic type. A clinicopathologic study of 84 cases with suggested criteria for intermediate lymphocytic lymphoma. Cancer 41:1440–1455

    Article  CAS  PubMed  Google Scholar 

  • Friedlander ML (1984) Prognostic variables in epithelial ovarian cancer: A review. Aust NZ Obstet Gynecol 24:256–261

    Article  CAS  Google Scholar 

  • Fu YS, Huang I and Beaudenon S et al. (1988) Correlative study of human papillomavirus DNA, histopathology, and morphometry in cervical condyloma and intraepithelial neoplasia. Int J Gynecol Pathol 7:297–307

    Article  CAS  PubMed  Google Scholar 

  • Gallup DG and Corday DR (1979) Leiomyosarcoma of the uterus: Case reports and a review. Obstet Gynecol Surv 34:300–312

    Article  CAS  PubMed  Google Scholar 

  • Gerard-Marchant R, Hamlin I, Lennert K, Rilke F, Stansfeld AG and van Unnik JAM (1974) Classification of Non Hodgkin’s lymphoma. Lancet ii:406–408

    Google Scholar 

  • Gitstein S, Baratz M, David MP and Toaf R (1980) Endometrial stromatosis of uterus. A clinicopathological study of five cases. Gynecol Oncol 9:23–30

    Article  CAS  PubMed  Google Scholar 

  • Gloor E, Dialdes J, Hurlimann J, Ribolze J and Barrelet L (1983) Placental site trophoblastic tumor of the uterus with metastases and fatal outcome. Clinical and autopsy observations of a case. Am J Surg Pathol 7:483–486

    Article  CAS  PubMed  Google Scholar 

  • Graem N and Helweg-Larsen K (1979) Mitotic activity and delay in fixation of tumour tissue. Acta Pathol Microbiol Scand Sect A 87:375–378

    Google Scholar 

  • Griffin NR, Howard MR, Quirke P, O’Brien CJ, Child JA and Bird CC (1988) Prognostic indicators in centroblastic centrocytic lymphoma. J Clin Pathol 41:866–870

    Article  CAS  PubMed  Google Scholar 

  • Haapasalo H, Collan Y, Atkin NB, Pesonen E and Seppa A (1989a) Prognosis of ovarian carcinomas: prediction by histoquantitative methods. Histopathology 15:167–178

    Article  CAS  PubMed  Google Scholar 

  • Haapsalo H, Pesonen E and Collan Y (1989b) Volume corrected mitotic index (M/V index) – the standard of mitotic activity in neoplasms. Pathol Res Pract 185:551–554

    Google Scholar 

  • Haapasalo H, Collan Y, Seppa, Gidlund AL, Atkin NB and Pesonen E (1990) Prognostic value of ovarian carcinoma grading methods - a method comparison study. Histopathology 16:1–7

    Article  CAS  PubMed  Google Scholar 

  • Hacker NF, Berek JS, Lagasse LD, Nieberg RK and Elashoff RM (1983) Primary cytoreductive surgery for epithelial ovarian cancer. Obstet Gynecol 61:413–420

    CAS  PubMed  Google Scholar 

  • Hannigan EV and Gomez LG (1979) Uterine leiomyosarcoma. A review of prognostic clinical and pathologic features. Am J Obstet Gynecol 134:557–564

    CAS  PubMed  Google Scholar 

  • Hart WR and Billman JK (1978) A reassessment of uterine neoplasms originally diagnosed as leiomyosarcomas. Cancer 41:1902–1910

    Article  CAS  PubMed  Google Scholar 

  • Hemdal I and Frankendal B (1985) Letter to editor. (Comment on paper by Marchesse et al.) Gynecol Oncol 22:379–380

    Article  CAS  PubMed  Google Scholar 

  • Hermens AF and Barendsen GW (1969) Changes of cell proliferation characteristics in a rat rhabdomyosarcoma before and after X-irradiation. Eur J Cancer 5:173–189

    Article  CAS  PubMed  Google Scholar 

  • Kempson RL (1976) Mitosis counting II. Hum Pathol 7:482–483

    Article  CAS  PubMed  Google Scholar 

  • Kempson RL and Bari W (1970) Uterine sarcomas. Classification, diagnosis and prognosis. Hum Pathol 1:331–349

    Article  CAS  PubMed  Google Scholar 

  • King ME, Dickerson GR and Scully RE (1982) Myxoid leiomyosarcoma of the uterus. A report of six cases. Am J Surg Pathol 6:589–598

    Article  CAS  PubMed  Google Scholar 

  • Kurman RJ and Norris HJ (1976) Mesenchymal tumors of the uterus. VI. Epithelioid smooth muscle tumors including leiomyoblastoma and clear cell leiomyoma. A clinical and pathological analysis of twenty-six cases. Cancer 37:1853–1865

    Article  CAS  PubMed  Google Scholar 

  • Kurman RJ, Scully RE and Norris HJ (1976) Trophoblastic pseudotumor of the uterus. Cancer 38:1214–1226

    Article  CAS  PubMed  Google Scholar 

  • Lathrop JC, Lauchlan S, Nayak R and Ambler M (1988) Clinical characteristics of placental site trophoblastic tumor (PSTT). Gynecol Oncol 31:32–42

    Google Scholar 

  • Lipponen PK, Eskelinen M, Collan Y, Marin S and Alhara E (1990a) Volume-corrected mitotic index in human pancreatic cancer: relation to histological grade, clinical stage and prognosis. Scand J Gastroenterol 25:548–554

    Article  CAS  PubMed  Google Scholar 

  • Lipponen PK, Collan Y, Eskelinen M, Pesonen E and Sotarauta M (1990b) Volume-corrected mitotic (M/V index) in human bladder cancer: relation to histological grade (WHO), clinical stage (UICC) and prognosis. Scand J Urol Nephrol 24:39–45

    Article  CAS  PubMed  Google Scholar 

  • Malkasian GD, Melton J, O’Brien PC and Greene MH (1984) Prognostic significance of histologic classification and grading of epithelial malignancies of the ovary. Am J Obstet Gynecol 149: 274–284

    Article  PubMed  Google Scholar 

  • Marchesse MJ, Liskow AS, Crum CP, McCaffrey RM and Frick HC (1984) Uterine sarcomas: a clinicopathologic study, 1965–1981. Gynecol Oncol 18:299–312

    Article  Google Scholar 

  • Morimoto N, Ozawa M, Kato Y and Kuramoto H (1982) Diagnostic value of mitotic activity in endometrial stromal sarcoma. Report of two cases. Acta Cytologica 26:695–704

    CAS  PubMed  Google Scholar 

  • Norris HJ (1976) Mitosis counting III. Hum Pathol 7:483–484

    Article  CAS  PubMed  Google Scholar 

  • Norris HJ and Taylor HB (1966) Mesenchymal tumors of the uterus. I. A clinical and pathological study of 53 endometrial stromal tumors. Cancer 19:755–766

    Article  CAS  PubMed  Google Scholar 

  • Perrone T and Dehner LP (1988) Prognostically favourable “mitotically active” smooth muscle tumors of the uterus. A clinicopathologic study of ten cases. Am J Surg Pathol 12:1–8

    Article  CAS  PubMed  Google Scholar 

  • Piver MS, Rutledge FN, Copeland L, Webster K, Blumenson L and Suh O (1984) Uterine endolymphatic stromal myosis: a collaborative study. Obstet Gynecol 64:173–178

    Article  CAS  PubMed  Google Scholar 

  • Quinn CM and Wright NA (1990) The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applications as prognostic variables. J Pathol 160:93–102

    Article  CAS  PubMed  Google Scholar 

  • Ralfs I, Dawber R, Ryan T, Duffill M and Wright NA (1981) The kinetics of metaphase arrest in human psoriatic epidermis; an examination of optimal experimental conditions for determining the birth rate. Br J Dermatol 104:231–242

    Article  CAS  PubMed  Google Scholar 

  • Ranchod M and Kempson RL (1977) Smooth muscle tumors of the gastrointestinal tract and retroperitoneum. A pathologic analysis of 100 cases. Cancer 39:255–262

    Article  CAS  PubMed  Google Scholar 

  • Rappaport H (1966) Tumors of the haematopoietic system. In: Atlas of tumor pathology. Armed Forces Institute of Pathology Washington DC

    Google Scholar 

  • Richardson GS, Scully RE, Nikrui N and Nelson JH (1985) Common epithelial cancer of the ovary (first of two parts). N Engl J Med 312:415–424

    Article  CAS  PubMed  Google Scholar 

  • Rodenburg CJ, Cornelisse CJ, Hermans J and Fleuren GJ (1988) DNA flow cytometry and morphometry as prognostic indicators in advanced ovarian cancer: A step forward in predicting the clinical outcome. Gynecol Oncol 29:176–187

    Article  CAS  PubMed  Google Scholar 

  • Ronan SG, Han MC and Das Gupta TK (1988) Histologic indicators in cutaneous malignant melanoma. Semin Oncol 15:558–565

    CAS  PubMed  Google Scholar 

  • Sadler DW and Coghill SB (1989) Histopathologists, malignancies and undefined high power fields. Lancet i:785–786

    Article  Google Scholar 

  • Saksela E, Lampijien V and Procope BJ (1974) Malignant mesenchymal tumors of the uterine corpus. Am J Obstet Gynecol 120:452–460

    CAS  PubMed  Google Scholar 

  • Scully RE and Young RH (1981) Trophoblastic pseudotumor. A reappraisal. Am J Surg Pathol 5:75–76

    Article  CAS  Google Scholar 

  • Silverberg SG (1971) Leiomyosarcoma of the uterus. A clinicopathologic study. Obstet Gynecol 38:613–628

    Article  CAS  PubMed  Google Scholar 

  • Silverberg SG (1976) Reproducibility of the mitosis count in the histologic diagnosis of smooth muscle tumors of the uterus. Hum Pathol 7:451–454

    Article  CAS  PubMed  Google Scholar 

  • Simnett JD and Heppleston AG (1966) Cell renewal in the mouse lung. The influence of sex, strain and age. Lab Invest 15:1793–1801

    CAS  PubMed  Google Scholar 

  • Sorbe B, Frankendal B and Veress B (1982) Importance of histologic grading in the prognosis of epithelial ovarian carcinoma. Obstet Gynecol 59:576–582

    CAS  PubMed  Google Scholar 

  • Stansfeld AG, Diebold J and Noel H, et al. (1988) Updated Kiel classification for lymphomas. Lancet i:292–293

    Article  Google Scholar 

  • Start RD, Cross SS and Smith JFH (1990) Effect of delayed fixation in the assessment of tumour cell proliferation. J Pathol 161:183–184

    Article  CAS  PubMed  Google Scholar 

  • Swerdlow SH, Habeshaw JA, Dhaliwall HS, Lister TA and Stansfeld AG (1983) Centrocyte lymphoma: a distinct clinicopathologic and clinical entity. Am J Pathol 113:181–197

    CAS  PubMed  Google Scholar 

  • Taina E, Maenpaa J, Erkkola R, Ikkala J, Soderstrom O and Viitanen A (1989) Endometrial stromal sarcoma: a report of nine cases. Gynecol Oncol 32:156–162

    Article  CAS  PubMed  Google Scholar 

  • Tannock IF (1968) The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumour. Br J Cancer 22:258–273

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tannock IF (1970) Population kinetics of carcinoma cells, capillary endothelial cells and fibroblasts in a transplanted mouse mammary tumor. Cancer Res 30:2470–2476

    CAS  PubMed  Google Scholar 

  • Taylor HB and Norris HJ (1966) Mesenchymal tumors of the uterus. IV. Diagnosis and prognosis of leiomyosarcomas. Arch Pathol 82:40–44

    CAS  PubMed  Google Scholar 

  • Taylor JF, Iversen OH and Bjerknes R (1977) Growth kinetics of Kaposi’s sarcoma. Br J Cancer 35:470–478

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Thatcher SS and Woodruff JD (1982) Uterine stromatosis: a report of 33 cases. Obstet Gynecol 59:428–434

    CAS  PubMed  Google Scholar 

  • The Non-Hodgkin’s lymphoma pathologic classification project: National Cancer Institute sponsored study of classifications of Non-Hodgkin’s lymphoma (1982) Summary and description of a working formulation for clinical usage. Cancer 49:2112–2135

    Article  Google Scholar 

  • Tiltman AJ (1988) Muscle tumor mitoses. Am J Surg Pathol 12:967–968

    CAS  PubMed  Google Scholar 

  • Twiggs LB, Okagaki T, Phillips GL, Stroemer JR and Adcock LL (1981) Trophoblastic pseudotumor-evMence of malignant disease potential. Gynecol Oncol 12:238–248

    Article  CAS  PubMed  Google Scholar 

  • Wright NA (1984) Cell proliferation in health and disease. In: Anthony PP, MacSween RNM (eds) Recent advances in histopathology. Churchill Livingstone, Edinburgh, pp 17–33

    Google Scholar 

  • Wright NA and Alison M (1984) The biology of epithelial cell populations. Clarendon Press, Oxford

    Google Scholar 

  • Wright NA and Appleton DR (1980) The metaphase arrest technique. A critical review. Cell Tissue Kinet 13:643–663

    CAS  PubMed  Google Scholar 

  • Wright NA, Britton DC, Bone G and Appleton DR (1977) An in vivo stathmokinetic study of cell proliferation in human gastric carcinoma and gastric mucosa. Cell Tissue Kinet 10:429–438

    CAS  PubMed  Google Scholar 

  • Wright NA, Appleton DR, Marks J and Watson AJ (1979) Cytokinetic studies of crypts in convoluted human small intestinal mucosa. J Clin Pathol 32:462–470

    Article  CAS  PubMed  Google Scholar 

  • Yoonessi M and Hart WR (1977) Endometrial stromal sarcomas. Cancer 40:898–906

    Article  CAS  PubMed  Google Scholar 

  • Young RH and Scully RE (1984) Placental site trophoblastic tumor: current status. Clin Obstet Gynecol 27:248–258

    Article  CAS  PubMed  Google Scholar 

  • Zaloudek C and Norris HJ (1987) Mesenchymal tumors of the uterus. In: Kurman RJ (ed). Blaustein’s pathology of the female genital tract. Springer Verlag, New York, pp 373–408

    Chapter  Google Scholar 

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Authors
  1. C. M. Quinn
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  2. N. A. Wright
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Editor information

Editors and Affiliations

  1. Department of Histopathology, UMDS, St Thomas’ Hospital, London, SE1 7EH, UK

    Peter A. Hall BSc, MD, MRCPath (Professor of Histopathology) (Professor of Histopathology)

  2. Department of Histopathology, UMDS, Guy’s Hospital, London, SE1 9RT, UK

    David A. Levison MD, FRCPath (Professor of Histopathology) (Professor of Histopathology)

  3. Imperial Cancer Research Fund, Lincoln’s Inn Fields, London, WC2A 3PN, UK

    Nicholas A. Wright MA, MD, PhD, DSc, FRCPath (Director of Clinical Research, Professor and Director) (Director of Clinical Research, Professor and Director)

  4. Department of Histopathology, Royal Postgraduate Medical School, Hammersmith Hospital, London, W12 0NN, UK

    Nicholas A. Wright MA, MD, PhD, DSc, FRCPath (Director of Clinical Research, Professor and Director) (Director of Clinical Research, Professor and Director)

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© 1992 Springer-Verlag London

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Quinn, C.M., Wright, N.A. (1992). Mitosis Counting. In: Hall, P.A., Levison, D.A., Wright, N.A. (eds) Assessment of Cell Proliferation in Clinical Practice. Springer, London. https://doi.org/10.1007/978-1-4471-3190-8_5

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  • DOI: https://doi.org/10.1007/978-1-4471-3190-8_5

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  • Print ISBN: 978-1-4471-3192-2

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