Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future

Rosa, Stefano La

doi:10.1007/s12022-023-09755-3

Cited by 17 publications

(18 citation statements)

References 140 publications

(175 reference statements)

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“…Moreover, the expression levels were notably higher in metastatic renal cell carcinoma tissues compared to primary ones. Additionally, it has been noted that higher levels of Ki-67 expression correlate with poorer prognoses for patients [23]. PFN1 binds to various proteins in normal physiological activities and can connect extracellular signaling with the intracellular actin skeleton, including important physiological activities such as membrane transport, cell survival and proliferation, and transcription [24].…”

Section: Discussionmentioning

confidence: 99%

Correlation between Ki-67 or Profilin-1 Expression Levels, Clinicopathological Characteristics and Postoperative Prognosis in Patients with Bladder Cancer

2024

Ann Ital Chir

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Background: Bladder cancer is the most common malignancy of the urinary system, and the search for new and reliable biomarkers has important clinical significance for the personalized treatment of bladder cancer. This study aims to explore the correlation between nuclear proliferation antigen (Ki-67) or Profilin-1 (PFN1) levels, clinicopathological characteristics, and postoperative prognosis in patients with bladder cancer. Methods: Patients with bladder cancer who underwent transurethral resection of bladder cancer tumor in The Fourth Affiliated Hospital of Soochow University, hospital from January 2019 to January 2021 were selected as the study group (n = 60), and patients with benign lesions of bladder cancer during the same period were selected as the control group (n = 60). The expression of Ki-67 and PFN1 in tumor and bladder tissues of the two groups was analyzed. Ki-67 recorded the patient's pathological parameters and calculated the patient's postoperative prognosis. The correlation between Ki-67 and PFN1 expression levels, pathological parameters, and postoperative prognosis was analyzed. Results: The positive expression rates of Ki-67 and PFN1 in the study group were 63.33% and 73.33%, respectively, which were significantly higher than the positive expression rates in the control group (χ2 = 14.803, 17.757, p < 0.001). The positive expression rates of Ki-67 and PFN1 were related to histological grade, clinical stage, infiltration, and lymph node metastasis, and the differences were statistically significant (p < 0.05). Bladder cancer patients with non muscle-invasive bladder cancer (NMIBC), high-grade histological grade, Ta~T1 clinical stage, invasive, and lymph node metastasis have a higher Ki-67 positive expression rate than bladder cancer patients with muscle-invasive bladder cancer (MIBC), low-grade histological grade, T2~T4, non-invasive, and no lymph node metastasis. The high expression level of Ki-67 has little relationship with gender, age, tumor diameter, and vascular invasion (p > 0.05). The survival time and three-year survival rate of the Ki-67 positive expression group were significantly lower than those of the Ki-67 negative expression group (p < 0.05). The survival time and three-year survival rate of the PFN1 positive expression group were significantly lower than those of the PFN1 negative expression group (p < 0.05). Conclusion: The positive expression rates of Ki-67 and PFN1 in bladder tumor tissue are significantly higher than those in bladder tissue, and pathological pattern, histological grade, clinical stage, infiltration, and lymph node metastasis are related to the positive expression rates of Ki-67 and PFN1, and different genders, ages, tumors diameter and vascular invasion are not related to the positive expression rates of Ki-67 and PFN1. The survival time and three-year survival rates of bladder cancer patients with Ki-67 positive and PFN1 positive expression are shorter.

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Section: Discussionmentioning

confidence: 99%

Correlation between Ki-67 or Profilin-1 Expression Levels, Clinicopathological Characteristics and Postoperative Prognosis in Patients with Bladder Cancer

2024

Ann Ital Chir

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“…The perceived advantages and disadvantages of each counting method are summarised in Table 2. To date, manual counting is considered to be the gold standard method to count the Ki67 proliferation index in neuroendocrine neoplasms 5,10,11 . It is highly accurate, readily available, permitting inclusion/exclusion of specific areas and allowing case‐based adjustment of positive threshold.…”

Section: Discussionmentioning

confidence: 99%

“…To date, manual counting is considered to be the gold standard method to count the Ki67 proliferation index in neuroendocrine neoplasms. 5,10,11 It is highly accurate, readily available, permitting inclusion/ exclusion of specific areas and allowing case-based adjustment of positive threshold. The printed counting sheets and/or the snapshots of manual counting via imaging software (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Various digital image analysis platforms and machine learning (ML)-based algorithms have shown to be highly sensitive and specific to obtain an automatic reading of the Ki67 index in pancreatic neuroendocrine neoplasms and breast carcinomas. [5][6][7][8][9][10][11] The utility of these platforms in determining the Ki67 index in MTC is yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Ki67 proliferation index in medullary thyroid carcinoma: a comparative study of multiple counting methods and validation of image analysis and deep learning platforms

Nadeem,

Hanna,

Viswanathan

et al. 2023

Histopathology

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AimsThe International Medullary Thyroid Carcinoma Grading System, introduced in 2022, mandates evaluation of the Ki67 proliferation index to assign a histological grade for medullary thyroid carcinoma. However, manual counting remains a tedious and time‐consuming task.Methods and resultsWe aimed to evaluate the performance of three other counting techniques for the Ki67 index, eyeballing by a trained experienced investigator, a machine learning‐based deep learning algorithm (DeepLIIF) and an image analysis software with internal thresholding compared to the gold standard manual counting in a large cohort of 260 primarily resected medullary thyroid carcinoma. The Ki67 proliferation index generated by all three methods correlate near‐perfectly with the manual Ki67 index, with kappa values ranging from 0.884 to 0.979 and interclass correlation coefficients ranging from 0.969 to 0.983. Discrepant Ki67 results were only observed in cases with borderline manual Ki67 readings, ranging from 3 to 7%. Medullary thyroid carcinomas with a high Ki67 index (≥ 5%) determined using any of the four methods were associated with significantly decreased disease‐specific survival and distant metastasis‐free survival.ConclusionsWe herein validate a machine learning‐based deep‐learning platform and an image analysis software with internal thresholding to generate accurate automatic Ki67 proliferation indices in medullary thyroid carcinoma. Manual Ki67 count remains useful when facing a tumour with a borderline Ki67 proliferation index of 3–7%. In daily practice, validation of alternative evaluation methods for the Ki67 index in MTC is required prior to implementation.

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“…This relationship has been recognized by the World Health Organization (WHO), which in its 5th edition classification, proposed the term “carcinoid tumors with elevated mitotic counts and/or Ki67 proliferation rates” to describe tumors with high Ki67 indices 11 . Numerous studies have recommended the utilization of Ki67 immunohistochemistry for diagnostic testing of bronchial or lung biopsies 12 making Ki67 a critical indicator for tumor diagnosis and pathological grading. In clinical practice, patients with a high Ki67 index are usually associated with a poor prognosis 13 , 14 .…”

Section: Introductionmentioning

confidence: 99%

Effects of different KRAS mutants and Ki67 expression on diagnosis and prognosis in lung adenocarcinoma

Wang,

Dong,

Zheng

et al. 2024

Sci Rep

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Lung adenocarcinoma (LUAD) is a prevalent form of non-small cell lung cancer with a rising incidence in recent years. Understanding the mutation characteristics of LUAD is crucial for effective treatment and prediction of this disease. Among the various mutations observed in LUAD, KRAS mutations are particularly common. Different subtypes of KRAS mutations can activate the Ras signaling pathway to varying degrees, potentially influencing the pathogenesis and prognosis of LUAD. This study aims to investigate the relationship between different KRAS mutation subtypes and the pathogenesis and prognosis of LUAD. A total of 63 clinical samples of LUAD were collected for this study. The samples were analyzed using targeted gene sequencing panels to obtain sequencing data. To complement the dataset, additional clinical and sequencing data were obtained from TCGA and MSK. The analysis revealed significantly higher Ki67 immunohistochemical scores in patients with missense mutations compared to controls. Moreover, the expression level of KRAS was found to be significantly correlated with Ki67 expression. Enrichment analysis indicated that KRAS missense mutations activated the SWEET_LUNG_CANCER_KRAS_DN and CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2 pathways. Additionally, patients with KRAS missense mutations and high Ki67 IHC scores exhibited significantly higher tumor mutational burden levels compared to other groups, which suggests they are more likely to be responsive to ICIs. Based on the data from MSK and TCGA, it was observed that patients with KRAS missense mutations had shorter survival compared to controls, and Ki67 expression level could more accurately predict patient prognosis. In conclusion, when utilizing KRAS mutations as biomarkers for the treatment and prediction of LUAD, it is important to consider the specific KRAS mutant subtypes and Ki67 expression levels. These findings contribute to a better understanding of LUAD and have implications for personalized therapeutic approaches in the management of this disease.

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Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future

Cited by 17 publications

References 140 publications

Correlation between Ki-67 or Profilin-1 Expression Levels, Clinicopathological Characteristics and Postoperative Prognosis in Patients with Bladder Cancer

Correlation between Ki-67 or Profilin-1 Expression Levels, Clinicopathological Characteristics and Postoperative Prognosis in Patients with Bladder Cancer

Ki67 proliferation index in medullary thyroid carcinoma: a comparative study of multiple counting methods and validation of image analysis and deep learning platforms

Effects of different KRAS mutants and Ki67 expression on diagnosis and prognosis in lung adenocarcinoma

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