Carcinosarcomas and Related Cancers: Tumors Caught in the Act of Epithelial-Mesenchymal Transition

Abstract

In this review, we outline the biology and management of patients with carcinosarcomas and related malignancies, which are often included under the broader concept of sarcomatoid carcinomas. Carcinosarcomas are unusual tumors that are commonly gynecologic in origin, where they are referred to as malignant mixed Müllerian tumors, but may appear in any anatomic site. Although a variety of hypotheses have been presented as to the biphasic nature of these tumors, carcinosarcomas seem to represent the best example in human cancers of the concept of epithelial-mesenchymal transition (EMT), in which the two parts of the tumor are genomically related to one another, as opposed to the mesenchymal component that represents a second neoplasm or (benign) reactive process. In general, patients with carcinosarcomas fare worse than patients with carcinomas of the same anatomic site. Treatment paradigms for carcinosarcomas generally follow those of carcinomas of the same organ site, except where clinical trials provide more specific options. Agents that block or reverse EMT are worth examination in patients with carcinosarcoma and arguably may be even more effective in carcinomas, given evidence of dependence on EMT to generate successful metastases. Information about EMT may also inform other phase transitions in cancer, such as those between prostate or lung carcinoma and more aggressive tumors with neuroendocrine differentiation.

Phosphatidylinositol 3‐kinase pathway genomic alterations in 60,991 diverse solid tumors informs targeted therapy opportunities

“…A significantly greater number of samples and a higher proportion of carcinosarcomas of ovarian origin in our series may explain these differences. It is interesting to note our data suggesting that the PI3K landscape of alterations is more similar to that of uterine carcinomas than general sarcomas, reinforcing the biologic relatedness of both . An important difference was the greater number of AKT2 alterations in carcinosarcomas (12% vs 3% in uterine cancers in general vs 2% in solid tumors).…”

“…We included 297 samples (predominantly uterine [n = 178] and ovarian [n = 99] in origin), which represent the largest series of molecular‐profiled carcinosarcomas to date. These tumors are rare and usually have a worse prognosis compared with carcinomas of the same anatomic site, and scarce therapeutic options are available . The cBioPortal catalog included 78 patients with uterine carcinosarcomas and reported PI3K pathway alterations in 71% of samples .…”

Reply to “Primary cutaneous biphasic sarcomatoid basal cell carcinoma with myoepithelial carcinoma differentiation. Is it a new variant of sarcomatoid basal cell carcinoma or a collision tumor composed of a myoepithelial carcinoma and an incidental basal cell carcinoma?”

“…Carcinosarcomas represent the best examples of the concept of epithelial‐mesenchymal transition 10 . We agree with Tran that a common clonal origin of cutaneous carcinosarcoma is currently the most accepted hypothesis, 11 but we have to note that additional genetic alterations (not present in the epithelial component) are found in the sarcomatoid component 11 .…”

<p>Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma</p>

“…[36][37][38] Basically, the appearance of an additional sarcomatoid/ sarcomatous component in an otherwise conventional NSCLC is due to up-regulation of the epithelial-tomesenchymal transition (EMT) secondary to activation of genetic mechanisms generally associated with resistance to chemotherapy and tyrosine kinase inhibitors, such as KRAS mutations, c-MET gene alterations, overexpression of vimentin, ZEB1, Snail, MiR-34 coupled to downregulation of E-cadherin and expression of epithelial markers, miR-200, mutations of EGFR (Figure 1). 39…”