Journey of a cancer sample, part II
On a drizzly Monday afternoon, clinical pathologist Chin-Lee Wu sits down at an unoccupied desk a few feet away from one of the Broad’s bustling laboratories and gets ready to examine over 100 slides beneath a microscope. Chin-Lee is a surgical pathologist at Massachusetts General Hospital where he specializes in urological cancers, including prostate, kidney, and bladder cancers. For the last three years, he has also served as a consultant pathologist for the Broad, peering at prepared slides of cancer samples and making sense of the cellular disarray. (See more in the video below.)
Last week, I watched as research associate Clint Chalk prepared these slides from samples of lung tissue (read more). Today, Clint hands white, plastic boxes containing the carefully labeled slides to Chin-Lee. Each cancer sample slide is paired with a slide of “normal” tissue – healthy lung tissue collected from the same patient. These sample pairs – called tumor/normal pairs – will allow researchers to compare a cancer genome to a healthy genome and pinpoint the differences that allow cancer cells to multiply unchecked and protect them from death.
Before these genomes can be compared or even sequenced, however, scientists need confirmation that these cancer samples are indeed what they are reported to be. Chin-Lee checks every slide to confirm the diagnosis of each anonymous patient and to verify that each piece of tissue is indeed from the lung. This check is in place to prevent a mislabeled sample from going undetected.
Chin-Lee also analyzes the content of each tissue sample, estimating the percentage of tumor cells on each slide and the quality of the tissue itself. In the least ideal situation, a large portion of the sample may be dead tissue. In other cases, the tissue may be composed of only a small fraction of tumor cells and will not contain enough tumor DNA for sequencing.
Some forms of cancer tend to have sparse cancer cells. Researchers at the Broad Institute recently sequenced the genomes of multiple prostate cancer samples (read more here), a form of cancer in which tumor cells tend to be spread out, which makes getting enough cells for sequencing a challenge. Chin-Lee’s estimate will help researchers make decisions about the best approach to preparing and sequencing these lung cancer samples and could help them pick the samples that have the highest concentration of cancer cells, and therefore the best chance of success in sequencing.
Chin-Lee peers through the microscope’s eyepiece, adjusting the coarse and fine foci as he switches magnification. He pauses to take in the tissue’s landscape, judging how much of it has been taken over by cancer cells. After viewing each slide, Chin-Lee records his analysis and estimates electronically using the Broad’s LIMS (Laboratory Information Management System), a database that helps researchers in different groups at the Broad carefully track samples.
Now that Chin-Lee has confirmed the samples’ diagnoses and recorded the first clues about the their quality, the samples are ready to continue their journey through the Biological Samples Platform, and then onward toward sequencing.