No ReStinG in surgical oncopathology

Molecular oncology and prediction have become popular directions in the management of cancer which is now claimed to follow a personalized direction. However, in order to connect „this new roof with an older basement" it is necessary to check using main standard parameters in practice. No single receptor, mutated gene or signaling pathway can restore disorder in standard clinico-pathological data. There still remains a lot of space for no resting or „No ReStlnG" of surgical oncologists and pathologists. Examination of nodes (No), resection margins (Re), clinical stage (St) and investigation of grade (InG) remain crucial factors in treatment strategies and prognosis. The accuracy of these parameters influence clinical outcomes more than any modification in chemotherapy, biotherapy or introduction of any new marker. Controlled trials of any therapeutic regimen may be easily distorted in case of errors or absence of any of the four principal „No ReStlnG" parameters. In order to describe the current situation in the Czech Republic which may not be far from other European countries, I checked the reports on these four parameters for several frequently occurring cancers in the nationwidepopulation-based Czech National Cancer Registry (functional since 1977, almost 7.5 million reported cancer cases) for years 2004 and 2005:

A) Negative lymph node (No) status varied widely in 14 regionsranging from 12-33% in the case of colon carcinoma and 3-13% in the case of malignant melanoma. It is unlikely that the proportions of stages l-ll and III are so different between regions with comparable numbers of cases and without any organized selection. In both diagnoses the shift from stage II (with NO) to stage III (with N+) indicates adjuvant therapy.

B) Completeness of resection (Re), as classified by parameters RO, R1 or R2, was not reported for instance in 6% of breast, 12% of rectal, 18% of bronchogenic, 38% of pancreatic and 50% of hepatocellular carcinomas. Microscopic (R1) or macroscopic (R2) residual tumor will certainly dictate a postoperative therapeutic strategy different from RO.

C) Clinical stage (St) of malignant disease was not reported in 7% of malignant melanomas, 10% of breast, 15% of colorectal, 16% of uterine cervix, 18% of prostate, 18% of renal, 30% of bronchogenic and 48 % of pancreatic carcinomas, and 39% of soft tissue sarcomas. In this array of cancer diagnoses the unknown stages reflect both difficult and defective diagnostic efforts. However, an appropriate therapeutic strategy cannot be determined without knowing the stage of disease or estimate of treatment efficacy.

D) Investigation of tumor grade (InG) in terms of degree of malignancy or aggressiveness in each individual case involves several aspects from standard histological grading criteria in various tumor types to new panels for gene expression grading indices. The approach and results in each treatment center/hospital have become more dependent on pathological expertise and the use of newer molecular methods. For instance, it has been suggested according to gene expression arrays that breast cancers are classified as basal cell-like, HER2-like, luminal A and luminal B. However, these subtypes also correspond to different phenotypes as detected by ER, HER2 and p53 immu-nohistochemistry. On the other hand standard histological grading, despite its impact on prognosis and indication for adjuvant therapy, was missing for 23% of breast, 18% of colorectal, 24% of uterine cervix and 16% of bladder early stage carcinomas. In soft tissue sarcomas, where the clinical stage is determined by grading, the histological grade was not reported in 42% cases.

In conclusion, it needs to be stressed that new molecular markers and predictors can be effectively utilized only if the standard classification criteria of malignant tumors are not missing or ignored.