Explanations for the disparity include different cell monitoring methods (i.e., radiolabeling vs fluorescent tagging, respectively). In contrast to the above data, they found that the majority of cells not only survived, but extravasated.
Recently, however, Chambers, Groom, and colleagues have quantified tumor cell fate using an intravital microscopy accounting method ( 16, 17). Several other labs subsequently demonstrated that cell killing occurred because of sheer ( 12, 13) or immune selection ( 14, 15). Fidler showed, using radiolabeled tumor cells, that the vast majority did not survive in the circulation ( 8, 11). The fate of blood-borne tumor cells is somewhat controversial because of apparently contradictory experimental evidence. Myth #5: Extravasated cells are metastases In short, not all tumors are invasive and metastatic and less subjective criteria are needed. Some might argue that morphologic criteria are objective measures of malignancy however, the discordance between experienced pathologists for grading (and even diagnosis) can be great (e.g., ( 3- 5)), suggesting that those parameters might be more subjective in nature. Likewise, while invasion through a basement membrane is the hallmark which objectively defines malignancy, not all neoplasms are invasive (e.g., carcinoma in situ of the breast (DCIS), prostatic intraepithelial neoplasia (PIN)). Therefore, metastasis is not an inherent property of all neoplastic cells or even invasive cells. Some tumors are highly aggressive, forming secondary lesions with high frequency (e.g., small cell carcinoma of the lung, melanoma, pancreatic carcinoma) whereas, others are rarely metastatic despite being locally invasive (e.g., basal cell carcinomas of the skin, glioblastoma multiforme). Myth #2: Metastasis and invasion are equivalent phenotypes Five myths regarding metastasis have crept into the scientific and medical literature because of imprecise use of terminology. In order to build a definition of a metastasis, it is first essential to disavow misconceptions regarding antecedent steps and the outcomes. The data prompted the question: What constitutes a metastatic mass? Given that it is now increasingly possible to detect single cells at secondary sites, should staging criteria be modified to accommodate new methodology? In many cases, cells expressing metastasis suppressors disseminated with equal efficiency to the corresponding parental cells however, they failed to colonize secondary sites. The primary impetus for revisiting the definition of a metastasis is recent experimental data arising from characterization of metastasis suppressors. This chapter focuses on the definition of a metastasis (i.e., the product), rather than defining the process of cancer spread itself, although the two are inextricably linked.
One of the reasons metastasis is so difficult to define is that the same word describes the process and the outcome. Ultimately, there is honest disagreement among researchers, oncologists and pathologists about what constitutes a metastasis. Perhaps a new definition would not be needed were consensus about the properties of a metastasis self-apparent. What has prompted me to re-examine the definition of a metastasis?