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Akt/mTOR, STAT3, ERK, PD-L1 expression linked to DFSP development, progression

21 Oct 2018

Local recurrence or metastasis of dermatofibrosarcoma protuberans (DFSP) may be predicted by complex factors beyond fibrosarcomatous subtype, according to a recent study.

Moreover, development and/or progression of DFSP appear to be associated with expression of protein kinase B (Akt)/mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), extracellular signal regulated kinase (ERK) and programmed death ligand 1 (PD-L1).

Nine recurrent DFSPs had larger tumour size, deeper invasion beyond the subcutis and more diverse histologic subtype compared with 35 noncurrent DFSPs. The fibrosarcomatous subtype showed a high cyclin D1–positive index and frequent mitotic figures.

Two metastatic DFSPs (one each of the fibrosarcomatous and myxoid subtypes) revealed four and 11 instances of local recurrence, respectively. These DFSPs also demonstrated larger tumour size, deeper invasion beyond the subcutis and high expression of cyclin D1.

Expression of Akt/mTOR, STAT3, ERK and PD-L1 was none or low in the primary skin lesions and high in the corresponding metastatic sites. DFSP had more frequent expression of Akt/mTOR and ERK than did dermatofibroma.

In this study, the authors performed clinicopathologic and immunohistochemical analyses for 44 DFSPs having wide local excision and 92 dermatofibromas as controls to determine the features and key factors for adverse outcome in DFSP, as well as the implication of expression of Akt/mTOR, STAT3, ERK, cyclin D1 and PD-L1.

The study was limited by the lack of data on patients prior to hospital evaluation.

“Little is known regarding oncoproteins other than platelet-derived growth factor subunit B in DFSP. Moreover, the risk factors for worse prognosis are controversial,” the authors said.

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Most Read Articles
15 Mar 2019
Roche recently announced their targeted therapy combination pertuzumab (Perjeta®)-trastuzumab (Herceptin®) plus conventional chemotherapy for treatment of early breast cancer in those with a subtype known as HER2-positive. The combination was previously used in the metastatic breast cancer setting, where cancer had already spread. There, it was able to prolong cancer sufferers’ lives significantly. Because of its effectiveness, the two-drug combo is new available for treatment of early HER2-positive breast cancer to further reduce the risk of metastasis or cancer recurrence. HER2-positive breast cancers usually spread faster and affect younger women and make up about one quarter of all newly diagnosed breast cancers.