Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1993 Jul;143(1):99–104.

Regressing thin cutaneous malignant melanomas (< or = 1.0 mm) are associated with angiogenesis.

R L Barnhill 1, M A Levy 1
PMCID: PMC1886944  PMID: 7686347

Abstract

In previous studies, we have shown that angiogenesis is often first noted in cutaneous malignant melanomas (CMMs) under 1.0 mm in thickness. Because angiogenesis may signal a more aggressive tumor phenotype, it is important to establish the circumstances associated with onset of angiogenesis. In the present study, we have quantified tumor vascularity in a series of CMMs under 1.0 mm in thickness and either associated with or lacking histologic regression. Microvessels were identified with the lectin Ulex europaeus agglutinin I and the vessels in five fields counted within an ocular grid (area 7.84 x 10(-2) mm2) at 400 x magnification. CMMs (mean 0.48 mm) with regression had greater microvessel counts (27.2 +/- 5.1) compared with CMMs (mean 0.61 mm) without regression (mean 20.1 +/- 7.9) (P < 0.01). However, of particular interest, CMMs in the radial growth phase only and associated with regression (mean 0.40 mm) had strikingly greater vascularity (mean 28.7 +/- 6.9) versus radial growth phase CMMs (mean 0.44 mm) lacking regression (mean 16.4 +/- 6.6) (P = 0.0013). CMMs in the vertical growth phase (mean 0.81 mm) without regression had slightly less vascularity (mean 24.4 +/- 7.3) compared with vertical growth phase CMMs with regression (mean microvessels 27.2 +/- 5.1) (P = 0.1878) but significantly greater microvessels versus radial growth phase CMMs without regression (P = 0.0213). These results suggest that the onset of angiogenesis in thin CMMs is related to at least two phenomena: 1) inflammatory regression and 2) development of the vertical growth phase.

Full text

PDF
99

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnhill R. L., Fandrey K., Levy M. A., Mihm M. C., Jr, Hyman B. Angiogenesis and tumor progression of melanoma. Quantification of vascularity in melanocytic nevi and cutaneous malignant melanoma. Lab Invest. 1992 Sep;67(3):331–337. [PubMed] [Google Scholar]
  2. Barnhill R. L., Mihm M. C., Jr, Ceballos P. I. Angiogenesis and regressing cutaneous malignant melanoma. Lancet. 1992 Apr 18;339(8799):991–992. doi: 10.1016/0140-6736(92)91569-t. [DOI] [PubMed] [Google Scholar]
  3. Blessing K., McLaren K. M., McLean A., Davidson P. Thin malignant melanomas (less than 1.5 mm) with metastasis: a histological study and survival analysis. Histopathology. 1990 Nov;17(5):389–395. doi: 10.1111/j.1365-2559.1990.tb00757.x. [DOI] [PubMed] [Google Scholar]
  4. Carnochan P., Briggs J. C., Westbury G., Davies A. J. The vascularity of cutaneous melanoma: a quantitative histological study of lesions 0.85-1.25 mm in thickness. Br J Cancer. 1991 Jul;64(1):102–107. doi: 10.1038/bjc.1991.250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clark W. H., Jr, Elder D. E., Guerry D., 4th, Braitman L. E., Trock B. J., Schultz D., Synnestvedt M., Halpern A. C. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst. 1989 Dec 20;81(24):1893–1904. doi: 10.1093/jnci/81.24.1893. [DOI] [PubMed] [Google Scholar]
  6. Clark W. H., Jr, Elder D. E., Guerry D., 4th, Epstein M. N., Greene M. H., Van Horn M. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol. 1984 Dec;15(12):1147–1165. doi: 10.1016/s0046-8177(84)80310-x. [DOI] [PubMed] [Google Scholar]
  7. Cooper P. H., Wanebo H. J., Hagar R. W. Regression in thin malignant melanoma. Microscopic diagnosis and prognostic importance. Arch Dermatol. 1985 Sep;121(9):1127–1131. [PubMed] [Google Scholar]
  8. Fallowfield M. E., Cook M. G. The vascularity of primary cutaneous melanoma. J Pathol. 1991 Jul;164(3):241–244. doi: 10.1002/path.1711640309. [DOI] [PubMed] [Google Scholar]
  9. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990 Jan 3;82(1):4–6. doi: 10.1093/jnci/82.1.4. [DOI] [PubMed] [Google Scholar]
  10. Folkman J. What is the role of angiogenesis in metastasis from cutaneous melanoma? Eur J Cancer Clin Oncol. 1987 Apr;23(4):361–363. doi: 10.1016/0277-5379(87)90370-1. [DOI] [PubMed] [Google Scholar]
  11. Gromet M. A., Epstein W. L., Blois M. S. The regressing thin malignant melanoma: a distinctive lesion with metastatic potential. Cancer. 1978 Nov;42(5):2282–2292. doi: 10.1002/1097-0142(197811)42:5<2282::aid-cncr2820420528>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  12. Hubler W. R., Jr, Wolf J. E., Jr Melanoma. Tumor angiogenesis and human neoplasia. Cancer. 1976 Jul;38(1):187–192. doi: 10.1002/1097-0142(197607)38:1<187::aid-cncr2820380129>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  13. Kelly J. W., Sagebiel R. W., Blois M. S. Regression in malignant melanoma. A histologic feature without independent prognostic significance. Cancer. 1985 Nov 1;56(9):2287–2291. doi: 10.1002/1097-0142(19851101)56:9<2287::aid-cncr2820560924>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  14. Little D., Said J. W., Siegel R. J., Fealy M., Fishbein M. C. Endothelial cell markers in vascular neoplasms: an immunohistochemical study comparing factor VIII-related antigen, blood group specific antigens, 6-keto-PGF1 alpha, and Ulex europaeus 1 lectin. J Pathol. 1986 Jun;149(2):89–95. doi: 10.1002/path.1711490203. [DOI] [PubMed] [Google Scholar]
  15. McGovern V. J., Shaw H. M., Milton G. W. Prognosis in patients with thin malignant melanoma: influence of regression. Histopathology. 1983 Sep;7(5):673–680. doi: 10.1111/j.1365-2559.1983.tb02279.x. [DOI] [PubMed] [Google Scholar]
  16. McGovern V. J. Spontaneous regression of melanoma. Pathology. 1975 Apr;7(2):91–99. doi: 10.3109/00313027509092702. [DOI] [PubMed] [Google Scholar]
  17. Naruns P. L., Nizze J. A., Cochran A. J., Lee M. B., Morton D. L. Recurrence potential of thin primary melanomas. Cancer. 1986 Feb 1;57(3):545–548. doi: 10.1002/1097-0142(19860201)57:3<545::aid-cncr2820570323>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  18. Paladugu R. R., Yonemoto R. H. Biologic behavior of thin malignant melanomas with regressive changes. Arch Surg. 1983 Jan;118(1):41–44. doi: 10.1001/archsurg.1983.01390010031008. [DOI] [PubMed] [Google Scholar]
  19. Ronan S. G., Eng A. M., Briele H. A., Shioura N. N., Das Gupta T. K. Thin malignant melanomas with regression and metastases. Arch Dermatol. 1987 Oct;123(10):1326–1330. [PubMed] [Google Scholar]
  20. Sagebiel R. Regression and other factors of prognostic interest in malignant melanoma. Arch Dermatol. 1985 Sep;121(9):1125–1126. [PubMed] [Google Scholar]
  21. Shaw H. M., McCarthy S. W., McCarthy W. H., Thompson J. F., Milton G. W. Thin regressing malignant melanoma: significance of concurrent regional lymph node metastases. Histopathology. 1989 Sep;15(3):257–265. doi: 10.1111/j.1365-2559.1989.tb03076.x. [DOI] [PubMed] [Google Scholar]
  22. Shaw H. M., McCarthy W. H., McCarthy S. W., Milton G. W. Thin malignant melanomas and recurrence potential. Arch Surg. 1987 Oct;122(10):1147–1150. doi: 10.1001/archsurg.1987.01400220057011. [DOI] [PubMed] [Google Scholar]
  23. Slingluff C. L., Jr, Vollmer R. T., Reintgen D. S., Seigler H. F. Lethal "thin" malignant melanoma. Identifying patients at risk. Ann Surg. 1988 Aug;208(2):150–161. doi: 10.1097/00000658-198808000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Smith J. L., Jr, Stehlin J. S., Jr Spontaneous regression of primary malignant melanomas with regional metastases. Cancer. 1965 Nov;18(11):1399–1415. doi: 10.1002/1097-0142(196511)18:11<1399::aid-cncr2820181104>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  25. Srivastava A., Hughes L. E., Woodcock J. P., Shedden E. J. The significance of blood flow in cutaneous malignant melanoma demonstrated by Doppler flowmetry. Eur J Surg Oncol. 1986 Mar;12(1):13–18. [PubMed] [Google Scholar]
  26. Srivastava A., Laidler P., Davies R. P., Horgan K., Hughes L. E. The prognostic significance of tumor vascularity in intermediate-thickness (0.76-4.0 mm thick) skin melanoma. A quantitative histologic study. Am J Pathol. 1988 Nov;133(2):419–423. [PMC free article] [PubMed] [Google Scholar]
  27. Srivastava A., Laidler P., Hughes L. E., Woodcock J., Shedden E. J. Neovascularization in human cutaneous melanoma: a quantitative morphological and Doppler ultrasound study. Eur J Cancer Clin Oncol. 1986 Oct;22(10):1205–1209. doi: 10.1016/0277-5379(86)90322-6. [DOI] [PubMed] [Google Scholar]
  28. Stenzinger W., Brüggen J., Macher E., Sorg C. Tumor angiogenic activity (TAA) production in vitro and growth in the nude mouse by human malignant melanoma. Eur J Cancer Clin Oncol. 1983 May;19(5):649–656. doi: 10.1016/0277-5379(83)90181-5. [DOI] [PubMed] [Google Scholar]
  29. Søndergaard K., Hou-Jensen K. Partial regression in thin primary cutaneous malignant melanomas clinical stage I. A study of 486 cases. Virchows Arch A Pathol Anat Histopathol. 1985;408(2-3):241–247. doi: 10.1007/BF00707986. [DOI] [PubMed] [Google Scholar]
  30. Trau H., Rigel D. S., Harris M. N., Kopf A. W., Friedman R. J., Gumport S. L., Bart R. S., Grier W. R. Metastases of thin melanomas. Cancer. 1983 Feb 1;51(3):553–556. doi: 10.1002/1097-0142(19830201)51:3<553::aid-cncr2820510332>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  31. Warren B. A., Shubik P. The growth of the blood supply to melanoma transplants in the hamster cheek pouch. Lab Invest. 1966 Feb;15(2):464–478. [PubMed] [Google Scholar]
  32. Weidner N., Semple J. P., Welch W. R., Folkman J. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med. 1991 Jan 3;324(1):1–8. doi: 10.1056/NEJM199101033240101. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES