Human tissues rarelybehave in a set pattern, more so in the setting of pathology, where each tissue will behave and grow in a
different way to progress to a pathological morphology, The prostate cancer- specifically, adenocarcinoma of the prostate is one
such pathology that has a varied etiology- One of them being high fat diet and smoking. Other factors are genetic- hypermethylation
of the GSTP1 gene promoter being one of the early change; with high risk in families linked to the HPC1 (hereditaryprostate cancer
1) susceptibility locus in RNASEL.
Gleason grading has proved a reliable and clinically significant prognostic factor in numerous studies. The accuracy ranges from
40-90 percent to diagnose prostatic cancer- along with other parameters from biochemistryand radiology. There are other factors
like extraprostatic extension, seminal vesicle invasion, and regional lymph node metastases- these are also taken into account while
grading. It is one of the key variables in several well-established prognostic models. Accurate Gleason score, along with pathologic
stage and surgical margin, are important while planning for surgeryand therapy thereafter; like the planning of post–radical
prostatectomymanagement in patients with adenocarcinoma. Interobserver variability for Gleason score among pathologists, even
urologic pathologists, has been well documented.
The validityof gleason grade over the years has stood the test of time- however there are newer parameters to suggest and
diagnose prostatic cancer. These are all used for screening- PSA, MRI and 4k score test. The 4k score test is a new and novel
blood test byOPKO Lab, Nashville, TN that incorporates a panel of four kallikrein protein biomarkers (total PSA, free PSA, intact
PSA, and human kallikrein-related peptidase 2) ; this along with few other clinical information in an algorithm that provides a percent
risk for a high-grade (Gleason score ≥ 7) cancer on biopsy. The biopsy still remains the gold standard for diagnosis and is usually
taken in TURP procedure.
Over the years, the Gleason grading system has undergone several changes. Currently, Gleason total scores 2–5 are no longer
assigned and in practice the lowest total score is now assigned a 6, although the scale continues to range from 2 to 10. This leads
to a logical yet incorrect assumption on the part of patients that their Gleason 6 cancer is in the middle of the scale, triggering the
fear that their cancer is serious and the assumption that treatment is necessarydespite Gleason score 6 actuallybeing a favorable
risk. To address these issues, a new 5-grade group system has been developed: Grade Group 1 (Gleason score ≤6) Grade Group
2 (Gleason score 3+4 = 7) Grade Group 3 (Gleason score 4+3 = 7) Grade Group 4 (Gleason score 4+4 = 8) Grade Group 5
(Gleason scores 9 and 10)
The Gleason grade is one of the finest examples of mathematics playing a role in disease diagnosis.Consensus conferences,
continued education, and subspecialty certification maybe helpful to minimize interobserver variability further. It takes into account
the inconsistencies and variabilities of a trained pathologist while giving a score to grade prostatic cancer. The ultimate validation
of mathematics superseding the subjectivityof us humans, will come to fruition with exact quantification by trained neural networks
and their consistencies in multi center studies.
Author:
Aniruddha Mundhada
PG Department of Pathology
SRMC Chennai
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