4.6 Article

Image-matching digital macro-slide-a novel pathological examination method for microvascular invasion detection in hepatocellular carcinoma

Journal

HEPATOLOGY INTERNATIONAL
Volume 16, Issue 2, Pages 381-395

Publisher

SPRINGER
DOI: 10.1007/s12072-022-10307-w

Keywords

Hepatocellular carcinoma; Microvascular invasion; 3-Point baseline sampling protocol; 7-Point baseline sampling protocol; Imaging-matching digital macro-slide; Recurrence-free survival; Receiver operating characteristic curve; AFP; PIVKA-II

Funding

  1. Key Project of the National Natural Science Foundation of China [81730097]
  2. Science Fund for Creative Research Groups [81521091]
  3. National Natural Science Foundation of China [81602523, 82072618]
  4. Shanghai Municipal Health Bureau [SHDC2020CR1004A]

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This study demonstrates that the use of IDS, a novel pathological examination method combining macro-slide and whole-mount slide imaging, can enhance the detection rate of MVI in hepatocellular carcinoma (HCC) and improve the prediction of HCC prognosis. The study also identifies alpha-fetoprotein as a suitable and robust biomarker to recognize MVI false-negative patients in conventional pathological protocols.
Background Microvascular invasion (MVI) is a prominent risk factor of postoperative recurrence for hepatocellular carcinoma (HCC). The MVI detection rate of conventional pathological examination approaches is relatively low and unsatisfactory. Methods By integrating pathological macro-slide with whole-mount slide imaging, we first created a novel pathological examination method called image-matching digital macro-slide (IDS). Surgical samples from eligible patients were collected to make IDS. The MVI detection rates, tumor recurrence rates and recurrence-free survival were compared among conventional 3-Point and 7-Point baseline sampling protocols and IDS. Additionally, biomarkers to recognize MVI false negative patients were probed via combining conventional pathological sampling protocols and IDS. Receiver operating characteristic curve (ROC) analysis was used to obtain the optimal cutoff of biomarkers to distinguish MVI false negative patients. Results The MVI detection rates were 21.98%, 32.97% and 63.74%, respectively, in 3-Point, 7-Point baseline sampling protocols and IDS (p < 0.001). Tumor recurrence rate of patients with MVI negative status in IDS (6.06%) was relatively lower than that of patients with MVI negative status in 3-Point (16.90%) and 7-Point (16.39%) sampling protocols. Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) were selected as potential biomarkers to distinguish MVI false negative patients. Conclusions Our study demonstrated that IDS can help enhance the detection rate of MVI in HCC and refine the prediction of HCC prognosis. Alpha-fetoprotein is identified as a suitable and robust biomarker to recognize MVI false-negative patients in conventional pathological protocols.

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