1. FISH of urothelial cells
Vittorio Grazioli, MD
CEO – IMPACT LAB

2. The real cure of cancer is early diagnosis
Cancer is the uncontrolled growth and spread of cells which often invade surrounding tissue and can metastasize to distant sites.
Despite ever-increasing knowledge concerning the prevention and treatment of cancer, the number of new cases continues to grow each year.
Currently, effective treatment of cancer relies on its early and accurate diagnosis.

3. Dysplasia is the frontline of the war against cancer
Since 1932 (thanks to Dr. Broder) we have considered in situ carcinoma as cancer and, more recently, to recognize dysplasia as a pre-cancerous lesion.
Dysplasia is a sort of grey zone, in which both regression and progression are possible, depending on factors that may represent a selective advantage for cancer cells but which cannot be identified by means of conventional methods.

4. From chromosomal instability to chromosomal chaos

5. From chromosomal instability to chromosomal chaos
In the squamous epithelium (i.e. cervical, oral, anal) but also in the urothelial cells, the gain of chromosome 3 (whose 3q26 locus maps for telomerase) represents a selective advantage leading to cell immortalization and therefore to the progressive chromosomal chaos typical of cancer cells.

6. From chromosomal instability to chromosomal chaos
NORMAL CELL
TUMOR CELL

7. FISH Results - Negative Specimen
Cytology review of a normal urine specimen.
Normal specimen analyzed by FISH.

8. FISH Results - Positive Specimen
Cytology review of an abnormal urine specimen.
Same specimen analyzed by FISH.

9. WHAT DO WE NEED TO FISH Target DNA Probe Fluorescence microscope
Cytogeneticist 9

10. CYTOPATHOLOGIC CLASSIFICATION OF URINE CYTOLOGY
Koss Classification
Negative
Mild atypia
Moderate atypia, suspect low-grade tumor
Severe atypia, suspect high grade tumor
Positive
Rosenthal&Raab Classification
Negative
Benign cellular changes
Atypical,indeterminatefor neoplasia
Low grade neoplasia
High grade neoplasia
Classification used at IMPACT LAB
Negative
Mild/moderate atypia
Reactive
Cannot exclude low grade tumor
Atypia, suspect for urothelial neoplasm
Positive

11. DIAGNOSTIC CATEGORIES PREFERRED BY UROLOGISTS
NEGATIV FOR HGUC
SUSPICIOUS FOR HGUC
POSITIVE FOR HGUC

12. SHOULD WE ELIMINATE THE “ATYPICAL” CATEGORY ?
APPROX % OF URINE ARE CLASSIFIED AS ATYPICAL
THEREFORE, UP TO 80 % OF ABNORMAL URINE ARE CLASSIFIED AS ATYPICAL
SIGNIFICANT PROPORTION OF MALIGNANT CASES WOULD BE MISSED IF “ATYPIA” WAS ELIMINATED

13. FISH: PRE-ANALYTICAL ISSUES
PATIENT SELECTION
INFLAMMATION
SPECIMEN COLLECTION

14. FISH: REPORT READING
AT LEAST 50 (IDEALLY 100) ATIPYCAL CELLS EVALUATED
RESULT MUST BE QUANTITATIVE
> 5% POSITIVITY = > 60% RISK