Letter to the Editor: Origins of PSA Testing: The Conversation Continues


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As Drs. James Mohler and Donald Trump noted in their September 15 letter to The ASCO Post (“More Thoughts on PSA,” 3[14]:2, 2012), Richard Ablin, PhD, discovered a “prostate-specific antigen” of unknown properties, but his PSA is not the antigen in the PSA test we know today.

Since Dr. Ablin has not published a new peer-reviewed paper on PSA since the early 1970s, a letter by Papsidero et al1 published in the Journal of the National Cancer Institute in 1981—which addressed all claims raised in Dr. Ablin’s letter and the references cited there—remains valid. My colleagues and I wrote, “We have also endeavored to provide substantial biochemical and biophysical characteristics of the prostate antigen in order to augment its immunologic identity as a distinct prostate antigen. Although not available for the studies of Dr. Ablin and his colleagues, modern methods of physicochemical characterization are now necessary to avoid equivocal interpretations of data between laboratories pursuing common goals.”

This is especially true in light of the fact that, in reply to Dr. Ablin’s request for a PSA sample from Roswell Park Cancer Institute in 1979, my effort to exchange PSA reagents between the two laboratories was met with silence. Further, the purified PSA and anti-PSA antibody prepared by Roswell Park researchers have been available in the public domain since 1986; to date, Dr. Ablin has not made his PSA accessible to the scientific community.

Key Point

Dr. Ablin’s reading misses a key point. The “initial report by Chu” that he referred to in his September 15 reply letter was an abstract posted at the Federation Meetings in 1977.2 Two years later, in our peer-reviewed full-length paper, my colleagues and I clearly stated that “[a] preliminary report has been previously presented,” citing this abstract. As explained and discussed at length by Wang et al,3 purification of PSA was a complex task. Since posting the abstract, we had vastly revised, refined, and improved the procedure to obtain purified and homogeneous PSA with a molecular weight of 33-34 kDa. The contaminant proteins initially copurified with PSA that may have masked and protected the glycoprotein nature of PSA had been removed.

This was not a surprising observation at all. We trust that Dr. Ablin is quite aware of the well-known paper in which Papsidero et al reported that the molecular weight of serum-borne PSA is detected as 100 kDa, instead of 33-34 kDa.4 Refined techniques were needed to ascertain the antigen’s true molecular weight after removal of other serum protein complexed with circulating PSA.

Stated Goal

The development of a simple blood test for early detection of prostate cancer was the stated goal of my National Institutes of Health–funded research project.5 The prevailing view then was that most tumor-specific antigens, prostate tumor–specific antigen included, were membrane-bound and nonsecretory, and thus would not be good candidates for in vitro blood tests but were instead more suitable for therapeutic purposes.

In addition, as the promising results on PSA and PSA testing kept coming from our laboratories, my colleagues and I were focused on these fascinating new findings. Some of our Roswell Park colleagues further pursued the investigation of prostate tumor–specific antigen.

Dr. Ablin’s criticisms are unwarranted. Readers should base their judgment of his work solely on science and evidence and not on unsupported claims. ■

—T. Ming Chu, PhD, DSc
Chair Emeritus, Diagnostic Immunology Research
Roswell Park Cancer Institute

References

1. Papsidero LD, Kuriyama M, Wang MC, et al: Prostate antigen(s): Reply. J Natl Cancer Inst 67(5):992-993, 1981.

2. Wang MC, Valenzuela LA, Murphy GP, et al: Tissue specific and tumor specific antigens in human prostate. Fed Proc 36:1254, 1977.

3. Wang MC, Valenzuela LA, Murphy GP, et al: Purification of a human prostate specific antigen. Invest Urol 17:159-163, 1979.

4. Papsidero LD, Wang MC, Valenzuela LA, et al: A prostate antigen in sera of prostatic cancer patients. Cancer Res 40:2428-2432, 1980.

5. Kuriyama M, Wang MC, Papsidero LD, et al: Quantitation of prostate-specific antigen in serum by a sensitive enzyme immunoassay. Cancer Res 40:4658-4662, 1980.


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