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Much of the early work on the molecular biology ofoncogenesis was done with the RNA tumour viruses of birdsand rodents. Over the past few years it has been shown thatthe virally coded genes responsible for transformation arealmost certainly derived from eukaryotic cellular genes. Thecellular homologues of these genetic hitch-hikers picked upby RNA tumour viruses remain present in normal rodent andavian cells. Since no involvement of these viruses has been

convincingly demonstrated in most human cancers, theirrelation to clinical oncology has remained dubious. However,in a recenweries of experiments, homology has been shownbetween a bladder carcinoma human oncogene and thecellular homologue of the Harvey murine sarcoma virus. 6Similar homology was shown between a human lungcarcinoma oncogene and the transforming gene of Kirstenmurine sarcoma virus. 7

These results are of great biological interest, but have theyany clinical implications? Little is known about the productsof these cellular oncogenes, which must in turn be the triggersfor malignancy. If we could find ways to control theirfunction by drugs or other agents then we might discovernovel systems for treating cancer. In a particularly elegantstudy, DNA fragments from a rat neuroblastoma were trans-fected into a mouse fibroblast line.8 After two passages thetransfected mouse fibroblasts were injected into young miceand grew out as tumours. Antibodies appeared in the sera ofthese mice, which identified a polypeptide of about 185 000daltons in molecular weight. It is thought that this proteinwas encoded by the transforming sequence and that it maymediate the transformation process in the rat neuroblastoma.

Furthermore, this 185K molecule, like many viral trans-forming proteins, was a phosphoprotein. Indeed there is nowevidence that the likely protein product of the human bladderoncogene derived from the EJ cell line is a 21K phospho-protein. Several groups are now applying the new tools ofmolecular biology to study human oncogene products and theprospects for logically developed cancer treatments havesubstantially improved.

HOW TO ENSURE QUALITY

THERE is a risk that the current enthusiasm for external

quality-assessment schemes may distract attention from theother steps which laboratories must take to maintain theclinical value of their reports. The situation is aggravated bythe confusion between quality control, quality assessment,and quality assurance.;Some helpful guidance comes from the book Good

Manufacturing Practice,’ published for the pharmaceuticalindustry five years ago. Quality assurance, briefly, consists ofa total system of organised working and testing designed toensure the quality of the product: in the medical laboratorythis will usually be a report. Quality control is a much morerestricted term. It refers only to those tests and procedureswhich must be completed before a particular batch of resultsis issued. Proficiency testing is also part of quality assurancebut is quite distinct from quality control.A complete quality assurance programme consists of five

5. Bishop JM. Enemies within: the genesis of retro virus oncogenes. Cell 1981; 23: 5-6.6. Parada LF, Tabin CJ, Shih C, Weinberg RA. Human EJ bladder carcinoma oncogene

is homologue of Harvey sarcoma virus ras gene. Nature 1982; 297: 474-78.7. Rigby P. The oncogenic circle closes. Nature 1982; 297: 451-53.8. Prodhy LC, Shih C, Cowing D, Finkelstein R, Weinberg RA. Identification of a

phospho-protein specifically induced by the transforming DNA of rat neuro-blastomas. Cell 1982; 28: 865-71.

1. Editorial. Quality of performance in pathology laboratories. Lancet 1981; i:599.2. Department of Health and Social Security. Guide to good pharmaceutical

manufacturing practice. London: H. M. Stationery Office, 1977.

main phases-which in practice overlap somewhat. A testmust be designed to give reliable and useful results. It must bevalidated to ensure that it gives the same results as those of areference method and that they are applicable to clinical

problems. The third step, is to revalidate the test for use in theparticular laboratory under actual working conditions. Thisinvolves checking arrangements for collecting, storing, anddocumenting specimens and for the recording, scrutiny, andissue of results.

If these first three steps are gone through fully and perfectlyit is arguable that no further measures are required so long asthe procedures are unchanged. This is not a realistic

suggestion, in an imperfect world.With every batch of tests quality-control systems must

operate. These may include preparations of known potencyor positive and negative controls. A positive control should,in general, be as weak as the weakest positive one wants todetect, and negative controls should be preparationscontaining those substances most likely to give invalid false-positive results. A good control system takes into account thestability and reliability (or lack of them) of the test used. Itshould be sufficient to reassure the laboratory scientist andthe pathologist that results are valid but it must also berealistic. Even the best controlled Wassermann reaction willhave its biological false-positives; no amount of qualitycontrol will make a non-specific screening test specific.There are less obvious opportunities for quality control.

Laboratories must have procedures for verifying abnormalresults before issue. An unexplained thrombocytopenia mustbe checked by blood-film examination and by inspection ofthe specimen for tiny clots; a positive HBsAg screen must beconfirmed by neutralisation; and so on. If these proceduresare built in to the organisation of a laboratory in such a waythat reports cannot be issued until they have been completed,then they are part of quality control in its strict sense.The last part of quality assurance is monitoring of results.

Here there is no accept-or-reject decision. Sensitivity,specificity, precision, and accuracy must be examined as timepasses to ensure that the only trend is one of continuingimprovement. Whitehead and Woodford3 have contrastedinternal and external quality assessment. As internal

programmes allow repeated testing of material they are

particularly well adapted to measurement of precision(consistency of results). They are also useful where clinicalmaterial is scanty or unstable. A histopathologist can arrangeto have a battery of slides reread under code even when he hasinsufficient tissue for national distribution.External quality assessment relies heavily on stable

specimens. It is most effective at measuring the accuracy of alaboratory report. This may be judged against a referencemethod or simply against som kind of national (or other)consensus. Unfortunately, external quality assessment

schemes rely on rather infrequent tests in each laboratory;thus it is never clear whether a bad result is caused byimprecision or inaccuracy, or by a combination of reasonableprecision, reasonable accuracy, and bad luck.

Finally the pathologist must talk to the clinicians. Did thereport arrive in time? Did it arrive at all? Was the reportlegible and comprehensible? Did it help? A wholeheartedpursuit of quality offers the medical laboratory scientist andthe pathologist an opportunity to raise their complementaryskills for the benefit of patients.

3. Whitehead TP, Woodford FP. External quality assessment of clinical laboratories inthe United Kingdom. J Clin Pathol 1981; 34: 947-57