Discrepant Estrogen Receptor Protein Levels According to Surgical Technique
Laurie J. Rosenthal, MD, FACS, FRCS(C), New York, New York
Determination of estrogen receptor protein levels in breast carcinoma tissue has become an important factor in the rational formulation of treatment plans for individual patients. The presence of estrogen receptors in a given specimen correlates directly with the patient’s response to hormonal manipulation [I]. A relation between the presence of estrogen receptor protein and anticipated response to chemotherapy may also exist [2,3]. Over a 6 month period 52 biopsy specimens of breast carcinoma tissue excised using scalpel dissection were assayed for estrogen receptor protein and revealed a positivity rate of 53 per cent. During the same time, 22 patients underwent breast biopsy for carcinoma; excision was accomplished largely by electrodissection, and hemostasis was achieved by electrocoagulation. The group of patients thus treated manifested an estrogen receptor protein positivity rate of 27 per cent. Estrogen receptor protein is characterized by heat lability , and technical considerations to ensure accuracy and reproducibility of results have dictated that tumor specimens be cooled after excision and transported stored in ice. The aforementioned disparate results prompted the belief that electrodissection resulted in denaturation of estrogen receptor protein, probably by heat exposure. This suspicion was confirmed. Material and Methods Two patients with tumors larger than 4 cm were anes-
thetized, and excisional biopsy using conventional scalpel dissection was performed. The excised specimen was then cut using a scalpel to yield two cubes of tumor tissue, 1 cm in each dimension, from immediately adjacent portions of the central part of the tumor. All remaining excised tissue From the Department of Surgery and the Surgical LipidLaboratory, Ths Mount Sinai Medical Center, New York, New York. Reprint requests should be addressed to Laurie J. Rosenthal, MD, The Mount Sinai Medical Center, 100 Street and Fifth Avenue, New York, New York, 10029.
was sent for pathologic examination by frozen section. One of the tissue specimens was immediately packed in ice. The second specimen was touched with the electrocautery scalpel on all surfaces, simulating excision of the tissue by electrodissection. The spark gap cutting current of the CSV Bovie Electrosurgical Unit (manufactured by LiebelFlarsheim Company) was used. The tissue was then immediately packed in ice. Estrogen receptor protein assay was carried out at 4’C following the dextran coated charcoal technique of McGuire and DeLaGarza  using Scatchard analysis  and the modification of Johnson et al . Results
The suspicion of infiltrating duct carcinoma was confirmed by frozen section examination in each case and the specimens for estrogen receptor protein determination were transported to the laboratory. Laboratory personnel were not informed which specimen had been exposed to electrodissection. Estrogen receptor protein assay is considered positive when greater than 10 femtomoles (fmol) of estradiol binding are present per milligram of cytosol protein. In the specimens studied, the estrogen receptor protein values for electrodissection and for scalpel technique, respectively, were as follows: case 1, 6 and 80 fmols/mg, and case 2, 3 and 20 fmols/ mg. Comments
In each case, estrogen receptor protein assay was negative in the specimen treated with electrodissection but positive in the tissue excised by scalpel. The findings were so strikingly different that no further cases were studied, and the Surgical Lipid Laboratory now requires that electrocautery be avoided in obtaining tissues for estrogen receptor protein assay. It is apparent that marked denaturation of estrogen receptor protein occurs when the specimen is
The American Journal of Surgery
exposed to electrodissection. That estrogen receptor protein was preserved at all despite the use of this technique in 27 per cent of specimens so treated no doubt reflects incomplete heat penetration through larger tumors. For accurate determination of estrogen receptor protein, it is essential that electrodissection and electrocoagulation be avoided during excision of the tumor specimen. Summary A marked discrepancy in the positivity rate of estrogen receptor protein assessment in breast biopsy specimens obtained by conventional scalpel dissection (53 per cent) and by electrodissection (27 per cent) raised the question of whether the latter technique was appropriate for obtaining specimens for estrogen receptor protein assay. Two cases served as their own controls to demonstrate the inherent error in obtaining tissue by electrodissection. It is now urged that the electrocautery technique be avoided when tissue is obtained for estrogen receptor protein assay.
Volume 138, November 1979
the generous guidance and participation of Dr. Dara Panveliwalla of the Surgical Lipid Laboratory and Dr. Demetrius Pertsemlidis of the Department of Surgery of The Mount Sinai Medical Center. References 1. Jensen EV, Block GE, Smith S, Kyser K, DeSombre ER: Estrogen receptors and breast cancer response to adrenalectomy. Nat/ Cancer lnst Monogr 34: 55, 197 1. 2. Kiang DT, Frenning DH, Goldman Al, Ascensao VF, Kennedy BJ: Estrogen receptors and responses to chemotherapy and hormonal therapy in advanced breast cancer. N Engl J Med 299: 1330.1978. 3. Lippmann ME, Allegra JC, Thompson EB, Simon R, Barlock A, Green L, Huff KK, Do HMT, Aitken SC, Warren R: The relation between estrogen receptors and response rate to cytotoxic chemotherapy in metastatic breast cancer. N Engl J Med 298: 1223, 1978. 4. McGuire WL, DeLaGarza M: Improved sensitivity in the measurement of estrogen receptor in human breast cancer. J C/in Endocrinol Metab 37: 986, 1973. 5. Scatchard G: The attractions of proteins for small molecules and ions. Ann NYAcad Sci 51: 660, 1949. 6. Johnson RB Jr, Nakamura RM, Libby RM: Simplified Scatchard plot assay for estrogen receptor in human breast tumor. C/in Chem 21: 1725, 1975.