DNA Specimen Provenance Assignment

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DNA Specimen Provenance Assignment (DSPA) also known as DNA Specimen ProvenanceAssay, is a molecular diagnostic test used to definitively assign biopsy specimen identity and establish specimen purity during the diagnostic testing cycle for cancer and other histopathological conditions. The term first appeared in the 2011 scientific paper, “The Changing Spectrum of DNA-Based Specimen Provenance Testing in Surgical Pathology,” published in the American Journal of Clinical Pathology, [1] which built upon concepts described in an earlier paper published in the Journal of Urology. [2]

Contents

Testing description

A panel of 16 microsatellite short tandem repeat (STR) markers that recognizes highly variable loci of human DNA is used in a PCR-based assay and analyzed by capillary electrophoresis. The 16 STR loci range from approximately 75 to 400 base pairs in length, and are highly polymorphic in the human population. The collective data from this panel provides a genetic profile, or ‘DNA fingerprint,’ representing the individual. [3] To complete the diagnostic testing cycle for cancer, the genetic profile from the putative malignant specimen(s) is compared with the genetic profile derived from the patient’s DNA reference sample taken via cheek swab at the time of the biopsy procedure.

Indications

Conventional histopathology is inherently subject to a certain degree of ambiguity due to the possibility of Specimen Provenance Complications (SPCs) resulting from instances of specimen transposition, extraneous/foreign cell contamination or misidentification of cells used in clinical or anatomical pathology. These types of errors are considered the most rapidly growing category of malpractice claims involving pathologists, and most claims involve a specimen switch between patients. [4] In terms of frequency of occurrence, a 2013 study published in the American Journal of Clinical Pathology indicates that 0.93% of biopsies could be subject to an SPC. Furthermore, each case involves at least two individuals, so this error rate actually underestimates the percentage of patients potentially impacted by incidents of biopsy misidentification. [5]

If left undetected, SPCs can compromise diagnostic accuracy and patient safety, potentially leading to adverse results such as treatment when no malignancy is present or delayed intervention for an advancing cancer. A study published in the Journal of Urology in 2014 concluded that more than 1 in every 200 prostate biopsy patients is misdiagnosed due to undetected specimen provenance complications. [6] Additionally, in a study published in the American Journal of Clinical Pathology in 2015, the researchers at Washington University’s School of Medicine Genomics and Pathology Services center in St Louis, MO, determined that 2% of tissue samples received in their lab for next generation sequencing were contaminated by another person’s DNA to an extent to be clinically significant (i.e. greater than 5% of the sample was contaminated). [7]

DNA Specimen Provenance Assay (Assignment) (DSPA) testing provides a solution to the problem of SPCs by confirming the identity and purity of patients’ biopsy samples so the most appropriate course of action can be taken. It is particularly useful when laboratory findings are unexpected or discordant with the clinical findings, when treatment options include radical surgical, radiological or chemical therapies, or delayed detection can have a significant negative impact on patient outcomes. [8]

Availability

DNA Specimen Provenance Assay (Assignment) (DSPA) testing can be performed on specimens from a range of medical specialty areas, such as gastroenterology, obstetrics, pulmonology, radiology, urology, etc. Molecular methods are currently available to extract DNA from a variety of sources, including fresh tissue, formalin-fixed, paraffin-embedded tissue and cytology specimens/slides. A combination of DSPA with conventional histopathology increases the diagnostic sensitivity and accuracy of patients’ biopsy results. Strand Diagnostics manufactures the know error system, a biopsy collection system that incorporate the DSPA test as part of the standard biopsy evaluation process.

Coding

In 2012, the American Medical Association recognized the growing adoption of DSPA testing as physicians' standard of care by creating two new "Tier 1" molecular diagnostics CPT(R) codes as follows: 81265 Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen, and 81266 Comparative analysis using Short Tandem Repeat (STR) markers; each additional specimen.

Related Research Articles

<span class="mw-page-title-main">Urology</span> Medical specialty

Urology, also known as genitourinary surgery, is the branch of medicine that focuses on surgical and medical diseases of the urinary-tract system and the reproductive organs. Organs under the domain of urology include the kidneys, adrenal glands, ureters, urinary bladder, urethra, and the male reproductive organs.

<span class="mw-page-title-main">Pathology</span> Study of the causes and effects of disease or injury, and how they arise

Pathology is the study of disease and injury. The word pathology also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatment, the term is often used in a narrower fashion to refer to processes and tests that fall within the contemporary medical field of "general pathology", an area that includes a number of distinct but inter-related medical specialties that diagnose disease, mostly through analysis of tissue and human cell samples. Idiomatically, "a pathology" may also refer to the predicted or actual progression of particular diseases, and the affix pathy is sometimes used to indicate a state of disease in cases of both physical ailment and psychological conditions. A physician practicing pathology is called a pathologist.

<span class="mw-page-title-main">Prostate-specific antigen</span> Mammalian protein found in humans

Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the KLK3 gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland.

<span class="mw-page-title-main">Biopsy</span> Medical test involving extraction of sample cells or tissues for examination

A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is then fixed, dehydrated, embedded, sectioned, stained and mounted before it is generally examined under a microscope by a pathologist; it may also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous or inflammatory conditions.

<span class="mw-page-title-main">Fine-needle aspiration</span> Diagnostic medical procedure

Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin, hollow needle is inserted into the mass for sampling of cells that, after being stained, are examined under a microscope (biopsy). The sampling and biopsy considered together are called fine-needle aspiration biopsy (FNAB) or fine-needle aspiration cytology (FNAC). Fine-needle aspiration biopsies are very safe minor surgical procedures. Often, a major surgical biopsy can be avoided by performing a needle aspiration biopsy instead, eliminating the need for hospitalization. In 1981, the first fine-needle aspiration biopsy in the United States was done at Maimonides Medical Center. Today, this procedure is widely used in the diagnosis of cancer and inflammatory conditions. Fine needle aspiration is generally considered a safe procedure. Complications are infrequent.

<span class="mw-page-title-main">Bence Jones protein</span> Urinary protein

Bence Jones protein is a monoclonal globulin protein or immunoglobulin light chain found in the urine, with a molecular weight of 22–24 kDa. Detection of Bence Jones protein may be suggestive of multiple myeloma, or Waldenström's macroglobulinemia.

<span class="mw-page-title-main">Prostatectomy</span> Surgical removal of all or part of the prostate gland

Prostatectomy is the surgical removal of all or part of the prostate gland. This operation is done for benign conditions that cause urinary retention, as well as for prostate cancer and for other cancers of the pelvis.

<span class="mw-page-title-main">Prostate biopsy</span>

Prostate biopsy is a procedure in which small hollow needle-core samples are removed from a man's prostate gland to be examined for the presence of prostate cancer. It is typically performed when the result from a PSA blood test is high. It may also be considered advisable after a digital rectal exam (DRE) finds possible abnormality. PSA screening is controversial as PSA may become elevated due to non-cancerous conditions such as benign prostatic hyperplasia (BPH), by infection, or by manipulation of the prostate during surgery or catheterization. Additionally many prostate cancers detected by screening develop so slowly that they would not cause problems during a man's lifetime, making the complications due to treatment unnecessary.

<span class="mw-page-title-main">Sentinel lymph node</span> First lymph node to receive drainage from a primary tumor

The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph nodes are the target organs primarily reached by metastasizing cancer cells from the tumor.

Prostate cancer screening is the screening process used to detect undiagnosed prostate cancer in men without signs or symptoms. When abnormal prostate tissue or cancer is found early, it may be easier to treat and cure, but it is unclear if early detection reduces mortality rates.

<span class="mw-page-title-main">Urachal cancer</span> Medical condition

Urachal cancer is a very rare type of cancer arising from the urachus or its remnants. The disease might arise from metaplastic glandular epithelium or embryonic epithelial remnants originating from the cloaca region.

Lower urinary tract symptoms (LUTS) refer to a group of clinical symptoms involving the bladder, urinary sphincter, urethra and, in men, the prostate. The term is more commonly applied to men—over 40% of older men are affected—but lower urinary tract symptoms also affect women. The condition is also termed prostatism in men, but LUTS is preferred.

<span class="mw-page-title-main">PCA3</span> Non-coding RNA in the species Homo sapiens

Prostate cancer antigen 3 is a gene that expresses a non-coding RNA. PCA3 is only expressed in human prostate tissue, and the gene is highly overexpressed in prostate cancer. Because of its restricted expression profile, the PCA3 RNA is useful as a tumor marker.

Douglas S. Scherr, M.D. is an American surgeon and specialist in Urologic Oncology. He is currently the Clinical Director of Urologic Oncology at Weill Cornell Medicine. He also holds an appointment at the Rockefeller University as a Visiting Associate Physician. Scherr was the first physician at Cornell to perform a robotic prostatectomy as well as a robotic cystectomy.

In urologic pathology, atypical small acinar proliferation, is a collection of small prostatic glands, on prostate biopsy, whose significance is uncertain and cannot be determined to be benign or malignant.

Treatment for prostate cancer may involve active surveillance, surgery, radiation therapy – including brachytherapy and external-beam radiation therapy, proton therapy, high-intensity focused ultrasound (HIFU), cryosurgery, hormonal therapy, chemotherapy, or some combination. Treatments also extend to survivorship based interventions. These interventions are focused on five domains including: physical symptoms, psychological symptoms, surveillance, health promotion and care coordination. However, a published review has found only high levels of evidence for interventions that target physical and psychological symptom management and health promotion, with no reviews of interventions for either care coordination or surveillance. The favored treatment option depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors include the man's age, his general health, and his feelings about potential treatments and their possible side-effects. Because all treatments can have significant side-effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations.

Specimen provenance complications (SPCs) result from instances of biopsy specimen transposition, extraneous/foreign cell contamination or misidentification of cells used in clinical or anatomical pathology. If left undetected, SPCs can lead to serious diagnostic mistakes and adverse patient outcomes.

<span class="mw-page-title-main">Molecular diagnostics</span> Collection of techniques used to analyze biological markers in the genome and proteome

Molecular diagnostics is a collection of techniques used to analyze biological markers in the genome and proteome, and how their cells express their genes as proteins, applying molecular biology to medical testing. In medicine the technique is used to diagnose and monitor disease, detect risk, and decide which therapies will work best for individual patients, and in agricultural biosecurity similarly to monitor crop- and livestock disease, estimate risk, and decide what quarantine measures must be taken.

The Skid Row Cancer Study was a study conducted by urologist Perry Hudson on the homeless men of the Bowery, in Lower Manhattan. In the 1950s and 1960s, Hudson went to skid row, to convince men to volunteer for his study. More than 1,200 men were promised a clean bed, three free square meals a day and free medical care if they were found to have prostate cancer. Hudson's early experience with seeing patients dying at a tuberculosis hospital he was working at led him to develop an interest in prostate cancer. His discovery about the lack of information regarding treatment for the disease and medical training for rectal exams needed to diagnose the disease drove him to pursue research in prostate cancer.

PI-RADS is an acronym for Prostate Imaging Reporting and Data System, defining standards of high-quality clinical service for multi-parametric Magnetic Resonance Imaging (mpMRI), including image creation and reporting.

References

  1. ↑ Pfeifer, J; Zehnbauer B; Payton J (2011). "The changing spectrum of DNA-based specimen provenance testing in surgical pathology". American Journal of Clinical Pathology. 135 (1): 132–138. doi: 10.1309/ajcplno4pfvzva4p . PMID   21173135.
  2. ↑ Suba, EJ; Pfeifer JD; Raab SS (2007). "Patient identification error among prostate needle core biopsy specimens-are we ready for a DNA time-out". Journal of Urology. 178 (4): 1245–1248. doi:10.1016/j.juro.2007.05.152. PMID   17698125.
  3. ↑ Chakraborty, R; Stivers DN; Su B; et al. (1999). "The utility of short tandem repeat loci beyond human identification: implications for development of new DNA typing systems". Electrophoresis. 20 (8): 1682–1696. doi:10.1002/(sici)1522-2683(19990101)20:8<1682::aid-elps1682>3.0.co;2-z. PMID   10435432. S2CID   20609402.
  4. ↑ Troxel, DB (2004). "Errors in surgical pathology". American Journal of Surgical Pathology. 28 (8): 1092–1095. doi:10.1097/01.pas.0000126772.42945.5c. PMID   15252317. S2CID   28949653.
  5. ↑ Pfeifer, JD; Liu J (2013). "Rate of occult specimen provenance complications in routine clinical practice". American Journal of Clinical Pathology. 139 (1): 93–100. doi: 10.1309/ajcp50wezhwifciv . PMID   23270904.
  6. ↑ Wojno, K; Hornberger J; Schellhammer P; Dai M; Morgan T (2014). "The clinical and economic implications of specimen provenance complications in diagnostic prostate biopsies". Journal of Urology. 193 (4): 1170–7. doi:10.1016/j.juro.2014.11.019. PMID   25463992.
  7. ↑ Sehn, Jennifer; Spencer D; Pfeifer J; Bredemeyer A; Cottrell C; Abel H; Duncavage E (2015). "Occult Specimen Contamination in Routine Clinical Next-Generation Sequencing Testing". American Journal of Clinical Pathology. 144 (4): 667–674. doi: 10.1309/AJCPR88WDJJLDMBN . PMID   26386089.
  8. ↑ Suba, EJ; Pfeifer JD; Raab SS (2007). "Patient identification error among prostate needle core biopsy specimens-are we ready for a DNA time-out?". Journal of Urology. 178 (4): 1245–1248. doi:10.1016/j.juro.2007.05.152. PMID   17698125.
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