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Plain English summary of "Molecular testing for the clinical diagnosis of fibrolamellar carcinoma"

Published, September, 2017 in Modern Pathology

Currently, fibrolamellar hepatocellular carcinoma (FLHCC) is diagnosed based on the histology and morphology of the liver cells in tumor tissue, meaning pathologists examine the shape of the cells and what else is present in the tissue after surgery using a microscope to determine the type of tumor that was removed. Pathologists can also confirm diagnosis using immunohistochemistry based on morphology.  In other words, they can see if certain proteins found in fibrolamellar, like cytokeratin 7 and CD68, are more present by using antibodies that target these proteins.

Previous studies have shown that a fusion of part of the DNAJB1 gene and part of the PRKACA gene is present in the DNA of FLHCC tumors.

The authors of this paper propose another method to confirm diagnosis of FLHCC in addition to morphology of the cells and immunohistochemistry of the tissue based on the presence of this DNAJB1-PRKACA DNA fusion event in FLHCC tumors known as break-apart fluorescent in situ hybridization (break-apart FISH).

This is a technique that allows one probe made of a specific DNA sequence to emit green light when it binds to its complementary sequence and another probe made of a different specific DNA sequence to emit a red light when it binds to its separate complementary sequence in a cell.  When green and red light emit from the same place, it is visualized as a yellow light. When green and red light emit separately, the sequence has “broken-apart.”

The authors used probes made from the DNA sequence of the PRKACA gene; the probes use sequences of DNA that are next to each other in the PRKACA gene so when the PRKACA gene remains whole, the probes bind to it and yellow light is emitted, and when the PRKACA gene breaks apart, like it does with the DNAJB1-PRKACA fusion event in FLHCC, the probes bind and red or green light is emitted separately.

 The authors’ findings show that this method is a clinically useful tool to confirm the diagnosis of FLHCC, in addition to morphology and immunohistochemistry. More accurate diagnosis will aid in providing better treatment for patients.

 --Melissa Jarmel, Rockefeller University