Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer

Abstract

Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review

“…Surprisingly, HER2 overexpression is a well-known characteristic feature of luminal BC [10,71]. This is apparently in contrast with the results of our study [57,58] and previous studies on the role of HER2 in BC. However, HER2 was found to be overexpressed even in MIBC that contains micropapillary features, which harbors an aggressive biological behavior [72].…”

“…First, the studies by Chen et al [27] and Lim et al [51] set a cutoff of HER2 overexpression by IHC at 50%, and the third one used the Hercept-test (cutoff 10%). As a consequence, one would consider the 50% cutoff as more suitable in NMIBC; however, the 10% cutoff has been extensively applied so far [34,[55][56][57][58], yielding significant results in terms of association between HER2 overexpression and recurrencefree survival (RFS) and/or progression-free survival (PFS). Furthermore, molecular mechanisms other than gene amplification account for HER2 protein overexpression in a considerable proportion of BCs [32,43,52,59].…”

“…In a further study, the combination of more molecular markers (HER2 + microsatellite instability factors MLH1 and MSH2) predicted T1 highgrade BC outcome; moreover, the higher the number of altered markers the lower the disease-free survival and PFS [58].…”

Assessing treatment response after intravesical bacillus Calmette–Guerin induction cycle: are routine bladder biopsies necessary?

“…Efforts to predict response to BCG treatment also include the use of urinary and tissue molecular markers [24][25][26][27]. Unfortunately, none of them has yet entered routine clinical practice.…”

The role of molecular genetic alterations in sensitivity of the adjuvant intravesical therapy for non-muscle invasive bladder cancer

“…Кроме того, гиперэкспрессия HER-2 являлась предиктором выживаемости без прогрессирования и безрецидивной выживаемости у всей когорты пациентов, в то время как экспрессия MLH1 -предиктором выживаемости без прогрессирования только в группе пациентов, получавших БЦЖ-терапию. Таким образом, был сделан вывод о том, что уровень экспрессии MLH1, MSH2 и HER-2 находится в обратной корреляции с выживаемостью без прогрессирования и рецидивом НМРМП[51].РМП занимает 3-е место по частоте мутаций генов репарации среди других злокачественных опухолей. Однако эти мутации распределяются неравномерно в зависимости от типа повреждения, подтипа РМП, локализации в тех или иных генах.…”