Zeta’s Proliferation Cocktail – Dual Stain.
Zeta’s Proliferation Cocktail provides dual staining of PHH3 and Ki-67, offering high-resolution insight into cell proliferation dynamics, especially in oncologic pathology. These two markers target different phases of the cell cycle, and when used together, they enhance the accuracy, specificity, and interpretability of proliferation assessment in tumors.
The Proliferation Cocktail includes two recombinant antibodies to PHH3 and Ki-67. Phosphohistone H3 (PHH3) is a marker specific for cells undergoing mitosis. Serine 10 of Histone H3 is phosphorylated in association with mitotic chromatin condensation in late G2 and M phase of the cell cycle and thus, PHH3 can distinguish mitosis from apoptotic nuclei. High level of PHH3 is associated with increased mitotic count and with high Ki-67 expression. Ki-67 antigen is a nuclear, non-histone protein that is present in all stages of the cell cycle except G0. This characteristic makes Ki-67 an excellent marker for proliferating cells. The combination of PHH3 (red) and Ki-67 (brown) immunohistochemical staining is helpful in evaluation of tumor grade (neuroendocrine tumor), and malignancy (uterine smooth muscle tumors, CNS tumors, GIST, melanocytic tumors).
Zeta’s Proliferation Cocktail can help distinguish mitosis from general proliferation, where Ki-67 is expressed in all actively cycling cells, but cannot differentiate whether the cell is in G1 vs. M phase and pHH3 is phosphorylated specifically during mitosis, offering a precise count of mitotic figures. Dual staining allows for quantifying total proliferation (Ki-67)and identifying actively dividing (mitotic) cells (pHH3). This is especially useful in tumors where mitotic activity correlates with prognosis (e.g., neuroendocrine tumors, gliomas, melanomas).
The Proliferation Cocktail can improve accuracy in mitotic index assessment, where mitotic figures are notoriously hard to identify on H&E due to overlapping apoptotic bodies and dense chromatin artifacts. Zeta’s Proliferation Cocktail combines pHH3, which provides clean, chromatin-bound nuclear labeling, improving interobserver reproducibility with Ki-67, which ensures mitoses are contextualized within the proliferating cell population.
The Proliferation Cocktail also has applications in tumor grading and prognostic stratification where several tumor types use mitotic rate or Ki-67 index as part of their grading/staging criteria including neuroendocrine tumors (G1, G2, G3), lymphomas, gliomas, and melanomas. Dual staining helps reconcile discordant morphology vs marker expression, improving diagnostic confidence.
Zeta’s DUAL STAIN products provide more information from limited tissues, by seeing two related markers on the same slide while also allowing pathologists to see cellular localization and interaction within the tumor environment. Zeta uses one mouse and one rabbit recombinant monoclonal in each cocktail to allow for differential color results.
Zeta Corporation is a leader in recombinant monoclonal IVD antibodies for immunohistochemistry (IHC) offering 400+ tumor and tissue specific relevant products developed by a pathologist for pathologists. Visit Precision Recombinant Antibodies – IVD Antibodies – About Zeta Corporation (zeta-corp.com) to learn more about Zeta Corporation.