Conclusion

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Different growth patterns of primary and metastatic tumors are a reflection of different interactions of the cancer cells with the surrounding tissue structures. The observation of nonangiogenic growth patterns in human carcinomas challenges the hypothesis that tumor growth is always dependent on angiogenesis. It would be more correct to say that neoplastic growth depends on an adequate blood supply. If this can be obtained from a vascular bed that already exists, the tumor can grow without the formation of new blood vessels.

Glossary

Alveolar growth pattern: Nonangiogenic growth pattern described in primary nonsmall-cell lung cancer and in pulmonary metastases; tumor cells fill the alveoli and exploit the interalveolar capillaries for their blood supply.

Fibrotic focus: Focus of exaggerated reactive tumor stroma formation in the center of a carcinoma consisting of collagen, a variable number of fibroblasts, blood vessels, and inflammatory cells; practical histopatholog-ical surrogate marker of hypoxia-driven angiogenesis in breast cancer.

Nonangiogenic growth: Tumor growth without induction of angio-genesis in which tumor cells obtain adequate blood supply by exploiting a preexisting vascular bed.

Replacement growth pattern: Nonangiogenic growth pattern described in liver metastases; tumor cells replace the hepatocytes in the liver plates and exploit the sinusoidal blood vessels for their blood supply.

References

1. Vermeulen, P. B., Gasparini, G., Fox, S. B., Colpaert, C. G., Marson, L., Gion, M., Belien, J. A. M., de Waal, R. M. W., Van Marck, E. A., Magnani, E., Weidner, N., Harris, A. L., and Dirix, L. Y. (2002). Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur. J. Cancer 38, 1564-1579. Guidelines for the estimation of ongoing angiogenesis and the amount of blood vessels in a solid tumor, integrating new concepts and mechanisms of tumor vascularization.

2. Hasebe, T., Tsuda, H., Hirohashi, S., Shimosato, Y., Iwai, M., Imoto, S., and Mukai, K. (1996). Fibrotic focus in invasive ductal carcinoma: An indicator of high tumor aggressiveness. Jpn. J. Cancer Res. 87, 385-394. First report presenting the fibrotic focus as a prognostic factor in invasive breast carcinoma.

3. Pezzella, F., Pastorino, U., Tagliabue, E., Andreola, S., Sozzi, G., Gasparini, G., Menard, S., Gatter, K. C., Harris, A. L., Fox, S., Buyse, M., Pilotti, S., Pierotti, M., and Rilke, F. (1997). Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis. Am. J. Pathol. 151, 1417-1423. Investigation of the pattern of vascularization in a series of 500 lung carcinomas with the description of an alveolar growth pattern characterized by the lack of parenchymal destruction and absence of both tumor associated stroma and new vessels.

4. Vermeulen, P. B., Colpaert, C. G., Salgado, R., Royers, R., Hellemans, H., Van de Heuvel, E., Goovaerts, G., Dirix, L. Y., and Van Marck, E. A. (2001). Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia. J. Pathol. 195, 336-342. Description of different patterns of vascularization in liver metastases with identification of a growth pattern characterized by tumor cells replacing the hepatocytes in the liver plates and exploiting the preexisting sinusoidal blood vessels.

5. Colpaert, C. G., Vermeulen, P. B., Fox, S. B., Harris, A. L., Dirix, L. Y., and Van Marck, E. A. (2003). The presence of a fibrotic focus in invasive breast carcinoma correlates with the expression of carbonic anhy-drase IX and is a marker of hypoxia and poor prognosis. Breast Cancer Res. Treat. 81, 137-147.

6. Colpaert, C. G., Vermeulen, P. B., van Beest, P., Goovaerts, G., Weyler, J., Van Dam, P., Dirix, L. Y., and Van Marck, E. A. (2001). Intratumoral hypoxia resulting in the presence of a fibrotic focus is an independent predictor of early distant relapse in lymph node-negative breast cancer patients. Histopathology 39, 416-426.

7. Colpaert, C. G., Vermeulen, P. B., van Beest, P., Goovaerts, G., Dirix, L. Y., Harris, A. L., and Van Marck, E. A. (2003). Cutaneous breast cancer deposits show distinct growth patterns with different degrees of angiogenesis, hypoxia and fibrin deposition. Histopathology 42, 530-540.

8. Pastorino, U., Andreola, S., Tagliabue, E., Pezzella, F., Incarbone, M., Sozzi, G., Buyse, M., Menard, S., Pierotti, M., and Rilke, F. (1997). Immunocytochemical markers in Stage I lung cancer: Relevance to prognosis. J. Clin. Oncol. 15, 2858-2865.

Capsule Biography

Cecile G. Colpaert is a pathologist working in a teaching hospital. Her main interest is breast cancer and the application of research findings from the field of tumor biology in diagnostic pathology practice.

Peter B. Vermeulen is a diagnostic pathologist doing translational breast cancer research mainly focused on angiogenesis and tumor-stroma interactions.

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