Twenty-six surgical breast cancer specimens were subjected to multiple estrogen receptor (ER) assays with a microsample technique. In most tumors there were large variations in ER Levels in samples taken from different regions of the same tumor. After correction of individual samples for differences in carcinoma content, such variations were not abolished. Nine of the 26 breast cancers, although positive overall, were devoid of ER in some regions. For ER-positive tumors the average coefficient of variation (CV) for intra-tumor ER levels was 86% , with a range from 25% to 200%. This is well above the CV obtained with repeat samples of homogeneous tissue (14%). These results suggest that many ER-positive cancers may be composed of cells with a variety of ER levels. An assessment of individual intratumor ER variability may have biologic and clinical significance.

It has hecome increasingly evident during the course of studies on amphibian pigment cell migration arid diff ereiitiatioii (recently reviewed by Twitty, '49) that further progress requires a more intimate knowledge of the morphology and behavior of the individual cell. In the present investigation, undertaken in response to this need, the phase contrast microscope has proved to be an exceptionally valuable tool.It permits ready observation of many details ordinarily not visible in living cells and circumvents the production of artifacts resulting from fixation. Aforeover, inherent in this type of microscopy is the distinct advantage of being able to observe not only the static qualities of a cell, but to study, a s well, the various changes in morphology accompanying dynamic processes such as cell migration and differentiation.The author wishes to express his gratitude to Dr. Victor C. Twitty f o r suggesting this study and for advice and encouragement during the course of the work and preparation of the manuscript.lRevision of a thesis submitted in partial fulfillment of the requirements for

Forty‐milligram strips of malignant breast tissue were divided longitudinally into 20‐mg microsamples. Soluble protein concentration was determined for one‐half, and histologic evaluation for viable carcinoma content was made on its sister half. The correlation coefficient for 88 such comparisons was 0.330. This suggests that estrogen receptor (ER) assays that do not take into account the actual amount of carcinoma present in the sample may not permit reliable stratification of ER data. Using this technique, ER values obtained for 129 breast tumor microsamples were adjusted to reflect carcinoma content. A comparison of ER values before and after such adjustment revealed that the relative status of 73% was not significantly changed. The ER status of 27%, however, was changed sufficiently to be of potential clinical significance.

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