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

Sep 24, 2026

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Ki67 immunohistochemistry in neuroendocrine neoplasms provides a framework for diagnosis and prognostic assessment. Since its first demonstration in pancreatic NENs in 1996, evidence has expanded across neuroendocrine and endocrine tumors, showing diagnostic, prognostic, and predictive usefulness with differences by tumor site and type. Gut and pancreatic NENs require Ki67 evaluation; lung NEN diagnosis is recommended on biopsy. Other organs show no diagnostic role and prognostic relevance remains controversial, while specific grading or therapy selection uses Ki67.

LanguageEnglish

CategoryHealthcare

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Pages19

Reading Time48 min

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Abstract

Introduction

Ki67 Proliferative Index in Different Endocrine and Neuroendocrine Neoplasms

Pituitary Neuroendocrine Tumors (PitNETs)

Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future Stefano La Rosa1,2 Accepted: 31 January 2023 / Published online: 17 February 2023 © The Author(s) 2023 Abstract The introduction of Ki67 immunohistochemistry in the work-up of neuroendocrine neoplasms (NENs) has opened a new approach for their diagnosis and prognostic evaluation. Since the first demonstration of the prognostic role of Ki67 proliferative index in pancreatic NENs in 1996, several studies have been performed to explore its prognostic, diagnostic, and predictive role in other neuroendocrine and endocrine neoplasms. A large amount of information is now available and published results globally indicate that Ki67 proliferative index is useful to this scope, although some differences exist in relation to tumor site and type. In gut and pancreatic NENs, the Ki67 proliferative index has a well-documented and accepted diagnostic and prognostic role and its evaluation is mandatory in their diagnostic work-up. In the lung, the Ki67 index is recommended for the diagnosis of NENs on biopsy specimens, but its diagnostic role in surgical specimens still remains to be officially accepted, although its prognostic role is now well documented. In other organs, such as the pituitary, parathyroid, thyroid (follicular cell-derived neoplasms), and adrenal medulla, the Ki67 index does not play a diagnostic role and its prognostic value still remains a controversial issue. In medullary thyroid carcinoma, the Ki67 labelling index is used to define the tumor grade together with other morphological parameters, while in the adrenal cortical carcinoma, it is useful to select patients to treated with mitotane therapy. In the present review, the most important information on the diagnostic, prognostic, and predictive role of Ki67 proliferative index is presented discussing the current knowledge. In addition, technical issues related to the evaluation of Ki67 proliferative index and the future perspectives of the application of Ki67 immunostaining in endocrine and neuroendocrine neoplasms is discussed. Keywords Ki67 · Neuroendocrine neoplasms · Endocrine neoplasms · Prognosis · Classification Introduction The Ki67 antibody was created in 1983 by immunizing mice with nuclei of the Hodgkin lymphoma cell line L428 . It was called “Ki” referring to the city Kiel where the research team worked and “67” referring to the original clone in the 96-well plate [1] . Although the function of the identified protein was not known, it was immediately clear that it was involved in cell proliferation being detected in proliferating * Stefano La Rosa [stefano.larosa@uninsubria.it](stefano.larosa@uninsubria.it) 1 Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Via O. Rossi 9, Varese 21100, Italy 2 Unit of Pathology, Department of Oncology, ASST Sette Laghi, Varese, Italy normal and neoplastic cells. Unfortunately, the original Ki67 antibody only worked on frozen tissues and for this reason its use in routine practice was limited. Some years later, themonoclonal antibody MIB1, which works in formalin-fixed and paraffin-embedded tissues, was generated and since then the use of Ki67 immunohistochemistry in routine practice has become easy [2] . The prognostic role of Ki67 proliferative index in neuroendocrine tumors (NETs) was identified for the first time in 1996 by two independent Italian research teams [3, 4], and since then, many studies have been performed to evaluate its prognostic, diagnostic, and predictive role in other digestive neuroendocrine neoplasms (NENs). The encouraging results obtained in these investigations played a motor role to study the biological role of Ki67 in NENs located in other organs (i.e., pituitary, parathyroid, lung, etc.), but also in endocrine tumors such as follicular cell-derived thyroid tumors and adrenal cortical neoplasms. A large

FAQs

How does Ki67 immunohistochemistry contribute to neuroendocrine neoplasm assessment?

Ki67 immunohistochemistry supports diagnosis and prognostic evaluation by measuring proliferative activity. It also has predictive relevance across many neuroendocrine and endocrine tumors, though impact varies by tumor site and type.

Which tumor sites have a well-established diagnostic and prognostic role for Ki67?

Gut and pancreatic neuroendocrine neoplasms have a well-documented and accepted diagnostic and prognostic role, and Ki67 evaluation is considered mandatory in their diagnostic work-up.

Is the diagnostic role of Ki67 consistent across all organs?

No. In organs such as the pituitary, parathyroid, thyroid (follicular cell-derived neoplasms), and adrenal medulla, Ki67 does not play a diagnostic role, and its prognostic value is still controversial.

Sep 24, 2026

Uploaded by Logic