Circulating Polyploid Giant Cancer Cells, a Potential Prognostic Marker in Patients with Carcinoma

Abstract

Polyploid Giant Cancer Cells (PGCCs) have been recognized as tumor cells that are resistant to anticancer therapies. However, it remains unclear whether their presence in the bloodstream can be consistently detected and utilized as a clinical marker to guide therapeutic anticancer regimens. To address these questions, we conducted a retrospective study involving 228 patients diagnosed with six different types of carcinomas (colon, gastric, NSCLC, breast, anal canal, kidney), with the majority of them (70%) being non-metastatic. Employing a highly sensitive liquid biopsy approach, ISET^®, and cytopathological readout, we isolated and detected circulating PGCCs in the patients' blood samples. PGCCs were identified in 46 (20.18%) out of 228 patients, including in 14.47% of 152 non-metastatic and 29.85% of 67 metastatic cases. Patients were subsequently monitored for a mean follow up period of 44.74 months (95%CI: 33.39-55.79 months). Remarkably, the presence of circulating PGCCs emerged as a statistically significant indicator of poor overall survival. Our findings suggest that circulating PGCCs hold promise as a reliable prognostic indicator. They underscore the importance of further extensive investigations into the role of circulating PGCCs as a prognostic marker and the development of anti-PGCC therapeutic strategies to improve cancer management and patient survival.

Keywords: cancer giant cells; colon cancer; gastric cancer; liquid biopsy; lung cancer; polyploid giant cancer cells; prognostic marker.

Figure 1

Panel of pictures of Polyploid Giant Cancer Cells (PGCCs) from different types of carcinoma. (A) PGCCs from non-metastatic breast cancer patient stained with HER2 antibody revealed with 3,3′-Diaminobenzidine (DAB); (B) PGCCs of non-metastatic canal anal cancer, expressing PD-L1 and RAD23B antibodies revealed with DAB and Magenta chromogens, respectively; (C) PGCCs of non-metastatic canal anal cancer, stained with ERCC1 revealed with Magenta chromogen; (D) PGCCs derived from non-metastatic colon cancer stained with anti-TIMP and anti-MMP-2 revealed with DAB and Magenta chromogens, respectively; (E,F) Metastatic renal cancer PGCCs expressing BAP1 and NCAD, with the magenta chromogen used for both revelations; (G,H) PGCCs found in non-metastatic gastric cancer, expressing HER2 revealed with DAB chromogen; (I–K) PGCCs of metastatic NSCLC stained with TGFβRI and revealed with DAB chromogen; (L) PGCCs of metastatic NSCLC stained with EGFR and revealed with DAB chromogen; (M) PGCCs derived from metastatic NSCLC expressing CD47 revealed with DAB chromogen; (N) PGCC derived from metastatic NSCLC expressing TGFβRI and CD45 and revealed with DAB and magenta chromogens, respectively; (O) PGCCs of metastatic NSCLC without any staining, revealed by H&E. All images were taken at 400× magnification using a light microscope (Research System Microscope BX61-Olympus, Tokyo, Japan) coupled to a digital camera (SC100-Olympus, Tokyo, Japan). Morphological characteristics of PGCC are observed: cells with diameter more than 40 µm, high nuclei–cytoplasm ratio, mononucleated or multinucleated cells. The micropores, which are nominal 8 μm in diameter, of ISET^® membrane are identified by yellow asterisks.

Figure 2

Overall survival analysis in the whole group of patients. The PGCC presence is significantly associated with poor OS.

Figure 3

Overall survival analysis in the whole group of patients. The CTC presence with cut-off of 7 is significantly associated with poor OS (p = 0.048).

Figure 4

Overall survival. Association between PGCCs and poor OS in patients with colon cancer (p = 0.033).

Figure 5

Overall survival analysis in patients with colon cancer. The CTC presence with cut-off of 7 is significantly associated with poor OS (p = 0.017).

Figure 6

Patients’ inclusion. Flowchart showing the number of patients included per cancer type.