Significance of p53, p27, Ki-67, E-cadherin, and HER2 expression in upper urinary tract urothelial carcinoma

Missaoui, Nabiha; Bdioui, Ahlem; Baccouche, Atika; Belkacem, Oussama; Hmida, Wissem; Mokni, Moncef; Hmissa, Sihem

doi:10.1186/s43046-020-00047-z

Cited by 8 publications

(3 citation statements)

References 28 publications

(70 reference statements)

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“…In addition to TP53, ANXA10 expression was associated with a low Ki-67 LI. As a marker of cellular proliferation, high Ki-67 LI has been observed in 53–88% of UTUCs [32-35]. Previously, the high Ki-67 LI was found more frequently in T2-T4 tumors compared with Tis-T1 tumors and was correlated with adverse clinicopathological features, poor survival, and high risk of disease progression [33].…”

Section: Discussionmentioning

confidence: 99%

ANXA10 Expression Is Inversely Associated with Tumor Stage, Grade, and TP53 Expression in Upper and Lower Urothelial Carcinoma

Kobayashi¹,

Hayashi²,

Sentani³

et al. 2022

Pathobiology

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Introduction: Urothelial carcinoma (UC) is a common type of malignant disease, but little is known about the diagnostic and prognostic markers of upper urinary tract urothelial cancer (UTUC) because of its rarity. To clarify the significance of ANXA10 in UTUC, we studied ANXA10 expression with immunohistochemistry (IHC). Methods: The expression of ANXA10 was analyzed in the upper and lower urinary tract of UC by IHC in combination with The Cancer Genome Atlas (TCGA) data analysis. The association between ANXA10 expression and representative cancer-related molecules was also evaluated. Results: ANXA10 expression was weak in normal upper tract urothelium but was positive in 39/117 (33%) UTUCs. ANXA10 was more frequently positive in tumors with pure UC (36%, p < 0.05), papillary morphology (50%, p < 0.01), low grade (G1/2: 57%, p < 0.01), and pTa/is/1 stage (55%, p < 0.01) than in those with histological variants (0%), nodular morphology (9%), G3 (16%), and pT2/3/4 (13%), respectively. ANXA10-positive patients showed better cancer-specific survival and progression-free survival than ANXA10-negative patients (p < 0.05). IHC showed that ANXA10 positivity was detected more in cases with the low expression of TP53 (p < 0.01) and Ki-67 labeling index <20% (p < 0.01). In TCGA dataset of muscle-invasive bladder cancer, higher ANXA10 expression correlated with papillary morphology, lower grade/stage, luminal papillary subtype, wild-type TP53, and FGFR3 gene mutation. Conclusion: We revealed that ANXA10 expression was increased during carcinogenesis and was observed more frequently in papillary UC of lower grade and stage. However, its expression decreased as cancer progressed. Therefore, the ANXA10 expression in UTUC might be clinically useful for decision-making.

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Section: Discussionmentioning

confidence: 99%

ANXA10 Expression Is Inversely Associated with Tumor Stage, Grade, and TP53 Expression in Upper and Lower Urothelial Carcinoma

Kobayashi¹,

Hayashi²,

Sentani³

et al. 2022

Pathobiology

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“…Finally, 16 eligible studies were identified (Figure 1). [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] The main characteristics of the included studies, which were all retrospective, are summarized in Table 1 and Table 2. Among 16 studies, a total of 2030 UTUC patients ranging from 20 to 732 patients per study were reported.…”

Section: Study Selection and Characteristicmentioning

confidence: 99%

A systematic review and meta-analysis for human epidermal growth factor receptor 2 on upper tract urothelial carcinoma patients

Liao

et al. 2023

Tumori

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Objective: The expression and significance of human epidermal growth factor receptor 2 (Her2) in upper tract urothelial carcinoma (UTUC) remains controversial. Thus, we aimed to systemically review the Her2 expression in UTUC patients and its relationship with pathological characters and clinical outcomes with meta-analysis. Materials and methods: A systematically computerized search in PubMed, Scopus, Embase and Cochrane was conducted. From a total of 454 related articles, 35 articles were finally reviewed and 16 papers were chosen for further analysis. Pathological characters included tumor stage, grade, lymph node metastasis (LNM) and lymphovascular invasion (LVI). The clinical outcomes included overall survival (OS), recurrence-free survival (RFS), cancer specific survival (CSS), metastatic-free survival (MFS) and progression-free survival (PFS). RevMan software was used for meta-analyses. Results: In total 16 studies from 1994 to 2020 were chosen, 14 studies used immunohistochemistry to assess the expression of Her2 and 5 studies used in situ hybridization, with a positive rate of 0 to 74.0% and 7.2 to 18.1%, respectively. Her2-positive was significantly associated with stage (pooled HR 1.86; 95 % CI 1.43–2.42), grade (pooled HR 2.81; 95 % CI 1.01–7.85) and LNM (pooled HR 1.93; 95 % CI 1.18–3.15). However, there was no statistically relationship between Her2-positive with LVI (pooled HR 1.48; 95 % CI 0.64–3.46) and RFS (pooled HR 1.41; 95 % CI 0.98–1.83). Conclusions: This review indicated that UTUC patients with Her2-positive tended to develop higher stage and grade tumors and LNM. The Her2 expression in UTUC patients deserves further investigation in the future.

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“…15 ERBB2 mutations have also been found in some patients with refractory renal pelvis carcinoma. 16,17 Notably, bladder cancer patients with an ERBB2 mutation showed a favorable response to trastuzumab. 18,19 However, there are limited reports on the use of trastuzumab in renal pelvis carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Advanced renal pelvis carcinoma patient with an ERBB2 insertion mutation: a case report

Shang,

Lou,

Yin

et al. 2023

J Int Med Res

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The prognosis of renal pelvis cancer is poor and therapeutic options are limited, especially for patients with advanced disease. In this report, we present a case of advanced renal pelvis carcinoma in a male patient in his 60s, characterized by an activating mutation in ERBB2. Clinical evaluation resulted in a pathological diagnosis of renal pelvis carcinoma with liver metastasis. Immunohistochemistry staining results suggested that CK, P63, and PAX8 were positively expressed, while Sy, CK7, CK20, S100, PAX8, and HEP1 were negatively expressed. Furthermore, next-generation sequencing results showed an activating mutation in the ERBB2 gene. The patient initially received a trastuzumab-based combination therapy, which led to a significant reduction in ERBB2 mutation frequency and a stable condition after three treatment cycles. However, following continuous treatment for 4 months, the patient developed drug resistance that resulted in disease relapse. Subsequently, the patient received apatinib treatment, but the therapeutic response was not satisfactory. The patient’s condition underwent rapid deterioration and he ultimately succumbed to the disease. This case underscores the potential benefit of trastuzumab for treating ERBB2-mutated advanced renal pelvis cancer, but further highlights that overcoming drug resistance remains a crucial challenge for long-term efficacy.

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Significance of p53, p27, Ki-67, E-cadherin, and HER2 expression in upper urinary tract urothelial carcinoma

Cited by 8 publications

References 28 publications

ANXA10 Expression Is Inversely Associated with Tumor Stage, Grade, and TP53 Expression in Upper and Lower Urothelial Carcinoma

ANXA10 Expression Is Inversely Associated with Tumor Stage, Grade, and TP53 Expression in Upper and Lower Urothelial Carcinoma

A systematic review and meta-analysis for human epidermal growth factor receptor 2 on upper tract urothelial carcinoma patients

Advanced renal pelvis carcinoma patient with an ERBB2 insertion mutation: a case report

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