The Truth... What is it?





Breast Cancer Hormone Receptor Scoring

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I think that it is best for a pathologist to use "eyeballs" and instruments to help bracket cancers as to whether their receptor status is negative vs. weakly, moderately, or strongly positive & to include any considerations of homogeneity or heterogeneity. Four formal & "named systems" have been in use, all originally relying on some serious quantitative "eyeballing" as to prevalence & intensity. Let's begin with the informal, classical surgical pathology approach (which can be morphed with modern assessment):

  • the oldest is a comprehensive & quick "eyeball" assessment that includes intensity and prevalence of receptor IHC marking: either "flat out" negative, to mild (1+), moderate (2+), or strong (3+) "positivity". But, in 2011, I am suggesting another set of options short of the formal systems, below.
     
    prevalence:

    manual: a quick (not hasty) vs. thoughtful  "eyeball" estimate of % positive nuclei...this depends on retina sensitivity and brain
    computer assisted: carefully use VIAS or Virtuoso or some other system that counts % positive nuclei...this uses a light spectrum analysis segment defined by the manufacturer.

    intensity:

    manual: [note the intensity criteria in "H score, below; &, in doing true H scores for 2010, I note that 1+ is a narrow range of shades of IHC "marking", 2+ has a broad range of not-weak & not-densely-dark shades, and 3+ is a pretty narrow range] A quick (not hasty) vs. thoughtful  "eyeball" estimate of average intensity of nuclear stain. The "quick" (not hasty) is just a low to medium power quick judgment of weak, moderate, or strong intensity. The latter (thoughtful) means some expeditious but thoughtful thinking such as, "this all looks weak, 1+" vs. "this is weak but with some 2+ nuclei such that it seems about a third of the way between 1+ and 2+ or about 1.3+" vs. "this looks pretty strong & has enough 3+, 2+, and 1+ nuclei that I'm thinking that it is about halfway between 2+ & 3+ or about 2.5+. That estimate of average intensity number is then multiplied times the percentage of positive nuclei.

    computer assisted: as of 10/2013, I'm not aware of a computer system able to grade intensity.

    Magee Risk Calculator: HERE. This calculator uses tumor size, the 9-point scoring system for grade, Ki67 percentage, and quantitated ER, PR, and Heu-2. All of these can be gotten off of a very well done pathology report.

    the path report: in current times (2/2011) in general practice, I'm hoping that our group might at least use (1) the VIAS percentage & (2) one's "eyeball estimate" of mildly (in 1+ range), moderately (in 2+ range), and strong (in 3+ range) so as to actually report a diagnosis designation such as "ER strong 95%" in the path report diagnosis template. Short of using a formal system, as below, one might report an "informal H-score" (a "working man's H score") of % nuclear staining times either a "quick" vs. "thoughtful" eyeball estimate of intensity, as explained, above. Examples: let's say that ER by VIAS is 65%, quick eyeball intensity is 2+, and thoughtful eyeball intensity is 1.75+. The former gives an informal H score of 2 x 65 = 130; the latter gives an informal H score of 1.75 x 65 = 114 (both "moderate" intensity scores. Brackets: "mild" =1-99, "moderate"=100-199, & "strong" = 200-300.
      
     

19891, the "H score": sum (1) the percentage at each intensity (2) times each of 0-3+ intensity.
  

 percentage...multiplied by

 intensity level =

 Products to sum

 % fraction eyeballed as negative

 0

 

 % fraction eyeballed as weak

 1+ (weak color)

 

 % fraction eyeballed as distinct

 2+ (distinct color)

 

 % fraction eyeballed as dense-dark

 3+ (dense, dark, strong color)

 

 
(the above total 100%)

 

sum = _________________
(range 0-300)

   
   
19902, the "Quick score": the sum of % score plus intensity score
(range 0-7; 2-3=low, 4-5 =med., & 6-7=high).

 % staining SCORE

 % nuclei staining

 intensity SCORE

 est. average intensity

 1

 less than 10%

 1

 1

 2

 less than 30%

 2

 2

 3

 less than 70%

 3

 3

 4

 greater than 70%

 

 

   
              
  19964, the "Q score": the sum of % score plus intensity score.

 

% staining SCORE % nuclei staining intensity SCORE est. average intensity

0

0%

0

(none at all)

1

1-25%

1

(weak, see @ high power)

2

26-50%

2

(mod., see @ low power)

3

51-75%

3

(strong @ low power)

4

greater than 75%

 

 

 
     

  19983, the "Allred score": the sum of % score plus intensity score (range 0-8).


 % staining SCORE

 % nuclei staining

 intensity SCORE

 est. average intensity

 0

 none

 none

 0

 1

 less than 1 per 100

 1

 1

 2

 1-10%

 2

 2

 3

 10% to 1/3rd

 3

 3

 4

 between 1/3-2/3rds

 

 

 5

 > 2/3rds

 

 


                  
   
References:

  1. Kinsel LB, et. al., "Immunocytochemical Analysis of Estrogen Receptors as a Predictor of Prognosis in Breast Cancer Patients: Comparison with Quantitative Biochemical Methods", Cancer Research 49:1052-1056, 15 February 1989.
  2. Reiner A, et. al., "Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer", Cancer Research 50:7057-7061, 1 November 1990.
  3. Allred, DC, et. al. "Prognostic and predictive factors in breast cancer by immunohistochemical analysis", Modern Path. 11(2):155-168, 1998.
  4. Lee H., et. al., "The effect of fixation and processing on the sensitivity of oestrogen receptor assay by immunohistochemistry in breast carcinoma", J Clin Pathol, 55:236-238, 2002 [Qui J, et. al., "Effect of Delayed...in Breast Cancer", AJCP 134:813-819, 11/2010 & referring through ref. #5 to Barnes DM, et. al, "Immunohistochemical Determination...Breast Cancer Patients", Br. J. Ca. 74(9):1445-1451, Nov. 1996].

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(posted 31 October 2010; addition 10 December 2015)