Thebroad,long-?termgoalofthisprojectisconsistent,standardizeddiagnostictestingofsurgical specimensbyimmunohistochemistry(IHC).Themethodstoachievethisgoalarewellunderstoodinthe fieldofclinicallaboratorytesting:(1)standardizationofreagentsandprotocols,(2)automationto reducehumanerrors,and(3)theuseofstandardizedcontrolstoprovidetestperformancefeedback. Overthelasttwodecades,thefirsttwoofthesethreemethodswereimplementedforIHCtesting.This grantprojectfocusesonthethird-?-?standardizedIHCcontrols.Currentpracticeteachesnon- standardizedcontrols.Eachhistopathologylabtypicallyprocurestestcontrolsfromleftovertissue samplesinitsownparaffinblockarchives.Thisisastrikinglydifferentpracticefromclinicalblood laboratories,wherestandardizedandvalidatedcontrolsareproducedinlargequantitiesandsold throughcommercialvendors. Wehavedevelopedaninnovativetechnicalsolution,summarizedinaseriesofpublishedjournal articles.Overthelast2yearsandwithNCIfunding,ourbreastcancerIHControlsTMpanelforHER-?2,ER, andPRtestsrecentlyenteredclinicaltestingandwillbesubmittedforregulatoryclearancethisyear (2016). ThisDirect-?to-?PhaseIIproposaladdressesclinicalIHClaboratorypracticebeyondbreastcancer testing.WewillexpandtheIHControlsTMproductportfolio,from3analytes(HER-?2,ER,&PR)to30.The newIHControlsTMpanelscomprisetheGeneralPathology,Melanoma,LungCancer,andHematopathology testportfolios.Thisten-?foldexpansionisfeasiblewithfundingfromasinglePhaseIIgrantbecause:(a) wehavealreadyworkedoutthenuancesofproductdesign,manufactureundercGMP,andtesting,and (b)theadditionalanalyteswillmostlybeclassIproducts.
The SpecificAims ofthisproposalare:(1) creationofthenewIHControlsTMpanels,(2)analyticalvalidation,includingtestingforsensitivity, specificity,productstability,andmanufacturingreproducibility,and(3)clinicalvalidation,including testingforprecision,referenceinterval(expectedlevelofstaining),andlimitofdetection. Theapplicantgroupcomprisesabroad,multi-?disciplinaryteam,includingtheMDPR&Dteam, statisticalsupportfromtheTuftsClinical&TranslationalScienceInstitute(CTSI),surgicalpathologists, andconsultantsforregulatoryaffairs,qualitysystems,andIHCcommercialoperations.Converting clinicallaboratoriesfromhomebrewtostandardizedcontrolswillbeatransformativechange.
This project is to fund the development and clinical regulatory studies for a new, first-in- class, type of clinical test control in the field of (cancer) immunohistochemistry (IHC) testing. These clinical IHC test controls will solve an important problem in the field of cancer testing, relating to variability and inconsistency in IHC testing. Clinical test controls are important for promoting test reproducibility and consistency amongst hospital laboratories. These are the first standardized and quantificable IHC controls.
| Sompuram, Seshi R; Vani, Kodela; Schaedle, Anika K et al. (2018) Quantitative Assessment of Immunohistochemistry Laboratory Performance by Measuring Analytic Response Curves and Limits of Detection. Arch Pathol Lab Med 142:851-862 |
| Vani, Kodela; Sompuram, Seshi R; Schaedle, Anika K et al. (2017) The Importance of Epitope Density in Selecting a Sensitive Positive IHC Control. J Histochem Cytochem 65:463-477 |
| Vani, Kodela; Sompuram, Seshi R; Schaedle, Anika K et al. (2017) Analytic Response Curves of Clinical Breast Cancer IHC Tests. J Histochem Cytochem 65:273-283 |
