PMC9510919_01
Longitudinal progression of the cancer patient. (A) Timeline of diagnosis and treatment of the patient at different time intervals is illustrated. The primary laryngocarcinoma is diagnosed at t1, followed by detection of CTCs and CTECs at t3. A new malignant lesion in the pancreas is confirmed at t5. Detection of CTCs and CTECs at the end of therapy could effectively evaluate therapeutic efficacy, detect MRD, and predict early occurrence of malignancy. (B) Description of each time point from t1 to t10. (C) Continuous monitoring of CA19-9 and CEA. The patient has the highest concentration of CA19-9 at t5. The cut-off values of CA19-9 (37 U/ml) and CEA (5 ng/ml) are indicated by red and blue line, respectively. (D-G) Medical imaging. (Da, b) Abdominal CT scan shows no abnormality in pancreas. (Ea-d) Epigastric MRI, CE-MRI, MRCP and DWI indicate the metastatic pancreatic head carcinoma. (Ea) A space-occupying lesion in pancreas T2WI (red arrows). (Eb) An increase contrast signal in a space-occupying lesion in pancreas T1WI (red arrow). (Ec) A strong signal in a space-occupying lesion in pancreas T1WI by DWI (red arrow). (Ed) ADC imaging shows decrease signal in a space-occupying lesion in pancreas T1WI (red arrow). (F, G) A pancreatic space-occupying lesion with enhanced glycometabolism shown by PET-CT (red and white arrows).
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As depicted in  Figures 1A, B , a 57-year-old male was diagnosed with a primary hypolarynx squamous cell carcinoma (T2N1M0, stage III with a microinvasion) in July 2018 (t1). In February 2019 (t4), as depicted in  Figures 1   Ca, b , the follow-up examination showed an increased cancer antigen 19-9 (CA19-9) (161.42 U/ml, reference range: 0-37 U/ml) and carcinoembryonic antigen (CEA) (6.71 ng/ml, reference range: 0-5 ng/ml) for the first time. Additional abdominal color Doppler ultrasonography, abdominal CT scan ( Figures 1   Da, b ), epigastric contrast enhanced (CE) MRI, and magnetic resonance cholangiopancreatography (MRCP) all showed no abnormality in pancreas and other visceral organs. As illustrated in  Figures 1   Ea-d , epigastric MRI scan, CE-MRI, MRCP, and diffusion-weighted imaging (DWI) indicated the pancreatic head carcinoma. PET-CT in  Figures 1F, G  showed a pancreatic space-occupying lesion with enhanced glycometabolism.
Detection and molecular characterization of aneuploid CD31- CTCs and CD31+ CTECs performed by SE-iFISH. (A) Quantitative analysis of the detected CTCs and CTECs. Among 14 CTCs, 10 of them are large cells (10/14 = 71.4%), remaining 4 CTCs are in small cell size (28.6%). Different degrees of aneuploidy harbored by CTCs are trisomy 8 (35.7%), tetrasomy 8 (7.1%), and multisomy 8 (>=pentasomy 8, 57.1%), respectively. Most of detected 93 CTECs are large cells (89/93 = 95.7%), and the rest are small CTECs (4/93 = 4.3%). Degrees of aneuploidy in CTECs are 9.7% for triploidy, 4.3% for tetraploidy and 86% for multiploidy. n/c, not counted. (B) Representative images of the detected CTCs and CTECs. Ba, a large CTC with multiploid chr8 (CD31-/CD45-, >5 mm WBC size, LCTC
multi
). Bb, a small CTC with trisomy 8 (<=5 mm WBC, SCTC
tri
). Bc, a large tetraploid CTEC (CD31+/CD45-, LCTEC
tetra
) is indicated by a white arrow; a diploid CD45+ WBC is indicated by a red arrow. Bd, a small tetraploid CTEC (SCTEC
tetra
). Bars=5 mum.
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CD31- CTCs and CD31+ CTECs was performed according to the protocol at the end of combination regimens (t3, September 2018) in this case to evaluate surgery outcome and the therapeutic efficacy of the complete combination regimens. Comprehensive quantification and molecular characterization of aneuploid CTCs and CTECs were revealed in  Figure 2A . Representative images of CTCs and CTECs detected in this patient are demonstrated in  Figure 2B .