Original scientific paper

https://doi.org/10.20471/acc.2022.61.02.10

Urinary Bladder Cancer Recurrence and Expression of Lynch and HER Markers: Searching for Immunohistochemical Patterns among 113 Tumors from 33 Patients

Mate Matić ; Osijek Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; Department of Oncology, Osijek University Hospital Center, Osijek, Croatia
Branko Dmitrović ; Osijek Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; Department of Pathology and Forensics, Osijek University Hospital Center, Osijek, Croatia
Suzana Matić ; Osijek Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; Department of Ophthalmology, Osijek University Hospital Center, Osijek, Croatia
Sven Kurbel ; Osijek Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; Aviva Polyclinic, Zagreb, Croatia

Abstract

The aim was to identify immunohistochemical (IHC) markers able to predict
recurrence of urinary bladder tumors. The method of multivariate adaptive regression splines (MARS)
was applied to IHC data of 33 patients with urinary bladder cancer that relapsed one to six times (24
male and nine female, age 57-87 years). The MARS analysis was used to predict the total number of
recurrences and the Ki-67 value by nine IHC markers (epidermal growth factor receptor (EGFR),
HER2, HER3, E-cadherin, Ki-67, MLH1, MSH2, MSH6 and PMS2). Data were divided as initial
tumors, first and subsequent recurrences, and tumors that relapsed within nine months of previous
surgery or later. The IHC markers were semiquantitatively classified into four groups, as follows: 0
means no positive cells; 1, 10% of positive cells; 2, 11%-30% of positive cells; and 3, 31%-100% of
positive cells. In predicting the overall number of recurrences, as a surrogate marker of tumor biology,
the R2 value for all tumors was 0.423, for initial tumors 0.686, for first recurrence 0.700, and for subsequent
recurrences only 0.233. The key predictors for initial tumors were HER2 and MSH2, while
for the first recurrence it was EGFR. For quick recurrences (within nine months), the R2 was 0.474
with EGFR and HER3 as predictors, while for slow recurrences R2 was 0.640 due to EGFR and
PMS2. In predicting the Ki-67 value of that tumor, the R2 value for all tumors was 0.300, for initial
tumors 0.262, for first recurrence 0.360, and for subsequent recurrences only 0.533. The key predictors
for first recurrences were EGFR and MSH6, and for subsequent recurrences HER2, EGFR and all
Lynch markers. The R2 was 0.266 for quick recurrences and 0.370 for slow recurrences. The finding of
E-cadherin was not found relevant by any of these MARS models. In conclusion, the MARS results
associated multiple IHC markers with the number of recurrences and with Ki-67 values. It is important
that differences in predictive markers were found between initial tumors and first recurrences,
and between quick and slow recurrences, thus suggesting that tumor biology is different among these
subgroups regarding the total number of recurrences and Ki-67 values.

Keywords

Urinary bladder carcinoma; Immunohistochemistry; HER2; EGFR; Lynch markers; Ki-67; Tumor biology

Hrčak ID:

284738

URI

https://hrcak.srce.hr/284738

Publication date:

1.8.2022.

Article data in other languages: croatian

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