Isoantigens
A B H
Intraepithelial
in
Cervical
N e o p l a s i a
PATSY H. LILL, P H . D . , HENRY J. NORRIS, M.D., ALBERT I. RUBENSTONE,
M.D.,
MARY CHANG-LO, M.D., AND ISRAEL DAVIDSOHN, M.D.
Department of Experimental Pathology, Mount Sinai Hospital Medical Center, Chicago, Illinois ABSTRACT
T H E UTERINE CERVIX is commonly the site
of development of squamous-cell carcinoma. Because of its accessibility, the cervix lends itself to the study of the relationship of early lesions to the development of invasive carcinoma. T h e fates of early, benign, reversible lesions such as squamous metaplasia and the more ominous lesions such as severe dysplasia and carcinoma in situ have been widely studied. Received December 9, 1975; accepted for publication January 12, 1976. Supported in Part by Public Health Service Grant CA 17089-01 from the National Cancer Institute, and the Evelyn Steinberg Memorial Foundation, Chicago. Address reprint requests to Dr. Davidsohn: Department of Experimental Pathology, Mount Sinai Hospital Medical Center, California at loth St., Chicago, Illinois 60608. Dr. Lill's present address is: Basic Research, Frederick Cancer Research Center, Litton Bionetics, Inc., Frederick, Maryland. Dr. Norris is with the Armed Forces Institute of Pathology, Washington, D. C. Drs. Rubenstone and Chang-Lo are with the Department of Pathology and Dr. Davidsohn with the Department of Experimental Pathology, Mount Sinai Hospital Medical Center, Chicago, Illinois.
Studies by Christopherson and associates 1 indicate that eradication of dysplastic lesions would prevent the later development of invasive carcinoma. Richart and Barron 9 concluded that cervical neoplasia began as mild dysplasia and progressed to carcinoma in situ; however, the lesions were surgically removed at the carcinomain-situ stage so that no firm conclusion could be made as to their progression to invasive carcinoma. In their study only six of 463 women who had Class III Papanicolaou smears reverted to normal. In the remaining patients the cancers progressed to further classes or remained the same. Hall and Walton 6 reported that carcinoma in situ developed in 11.6% of a series of 206 women in whose cases the diagnosis of dysplasia had been made by biopsy, but 29.1% of those women had marked dysplasia. Green 5 reported that in a series of 142 patients who had basal-cell hyperactivity diagnosed by biopsy, 37% reverted
767
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Lill, Patsy H., Norris, Henry J., Rubenstone, Albert I., Chang-Lo, Mary, and Davidsohn, Israel: Isoantigens ABH in cervical intraepithelial neoplasia. Am J Clin Pathol 66: 767-774, 1976. T h e purpose of the study was to examine the relationship between the histologic findings and the presence or absence of ABH isoantigens in intraepithelial neoplasia of the cervix. After the lesions were graded by four pathologists, the Red Cell Adherence (RCA) test was done to demonstrate the ABH antigens, and the results of the two were compared. T h e correlation between the morphologic diagnosis and the results of the RCA test was limited. T h e percentages of tissues giving positive (+) or positive-negative (±) reactions were very similar in intraepithelial neoplasia (59.2%) and normal squamous epithelium (58.4%). T h e relationship of the RCA test results and behavior of the lesion was not studied. (Key words: Blood group antigens ABH; Cervix; Intraepithelial neoplasia; Immunopathology.)
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V* FIG. 1 (upper). A (left). Hematoxylin and eosin. Normal squamous epithelium of the cervix. B (right). RCA test. The epithelium is RCA-positive, with the exception of the basal cell layer, a consistent finding. Blood group B. FIG. 2 (middle). A (left). Hematoxylin and eosin. Moderate intraepithelial neoplasia of the cervix (arrow) (morphologic score 10). B (right). RCA test. An example of a (±) reaction. Positive reaction seen in deep squamous epithelium (arrow), whereas the surface is negative. Blood group B. FIG. 3 (lower). A (left). Hematoxylin and eosin. Normal squamous epithelium of the cervix. B (right). RCA test. Positive reaction seen only in the deeper layers. Blood group A.
November 1976
ISOANTIGENS ABH IN NEOPLASIA
769
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
to normal. The disparity in results may be Table 1. Comparison of Morphologic explained by the biopsies removing the and RCA Scores lesions. Richart 8 reported that a biopsy Number of Palienis Who site that includes both normal and cervical Had RCA Score* intraepithelial neoplasia will tend to be Morphologic re-epithelialized by normal epithelium. Score I II III Petersen 7 reported that in a series of 127 12 7/16 4 5 women who had epithelial hyperplasia with 11 1/11 4 6 nuclear abnormalities and borderline cases 10 4/16 7 5 9 3/12 6 3 followed for as long as 15 years, invasive S 4/8 2 2 carcinoma developed in 34 (29.9%). 7 2/5 1 9 6 1/2 — 1 The Red Cell Adherence (RCA) test2-3 5 3/8 2 3 demonstrated that normal squamous epi4 1/4 2 1 thelium of the cervix contained ABH anti3 6/10 2 9 2 gens, but in 89 of 102 cases (87%) of in1 — — — vasive carcinoma the antigen was no longer 0 demonstrable in the cancer cells, and in (Normal) 15/36 6 15 11 of 102 (11%) the antigen was reduced Squamous metaplasia 5/16 5 6 in amount, as evidenced by patchy side-byTotal number of cases: 144 side positive and negative reactions. In two * 1. positive; 11. positive and negative; ill. negative. cases (2%) of invasive carcinoma, the RCA test was positive. T h e present study was undertaken in an attempt to correlate the was examined separately by four pamorphology and the presence or absence thologists (Robert J. Kurman, M.D., and of the ABH antigens in intraepithelial authors A.I.R., M.C.-L., and H.J.N.) and neoplasia of the cervix. scored on a scale of 0 (normal) to 3 (severe intraepithelial neoplasia). T h e individual Materials and Methods scores given by the four pathologists to each One hundred fifty-five examples of slide were totaled so that the final morphocervical lesions from the files of the AFIP logic scores for individual sections ranged were chosen to represent in approximately from 0 to 12. Squamous metaplasia was equal numbers normal tissue, squamous identified as such without a number score metaplasia, mild intraepithelial neoplasia, assigned. Eleven sections were eliminated moderate intraepithelial neoplasia, and from the study due to breakage (4), imsevere intraepithelial neoplasia. No proper fixation (1) and inadequate material attempt was made to differentiate severe left in the block (6). intraepithelial neoplasia from carcinoma in situ. The term "intraepithelial neoMorphologic Score plasia" is used as a generic term to designate all the potential precursors to inIt seemed logical that the morphologic vasive cancer, including mild, moderate score best reflected the degree of intraand severe dysplasia and carcinoma in situ. epithelial neoplasia using the following: Because of possible inconsistency among 0 Normal epithelium pathologists in their interpretations of the 3-6 Mild intraepithelial neoplasia atypicality in intraepithelial lesions, a score, 7-10 Moderate intraepithelial neorather than a diagnosis, was assigned each plasia slide. One representative block of each case Severe intraepithelial neoplasia was chosen. At least four sections were cut 11-12 (ca-in-situ) serially from each block. One hematoxylin and eosin-stained section from each block After a score was obtained, two partici-
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A B H
Intraepithelial
in
Cervical
N e o p l a s i a
PATSY H. LILL, P H . D . , HENRY J. NORRIS, M.D., ALBERT I. RUBENSTONE,
M.D.,
MARY CHANG-LO, M.D., AND ISRAEL DAVIDSOHN, M.D.
Department of Experimental Pathology, Mount Sinai Hospital Medical Center, Chicago, Illinois ABSTRACT
T H E UTERINE CERVIX is commonly the site
of development of squamous-cell carcinoma. Because of its accessibility, the cervix lends itself to the study of the relationship of early lesions to the development of invasive carcinoma. T h e fates of early, benign, reversible lesions such as squamous metaplasia and the more ominous lesions such as severe dysplasia and carcinoma in situ have been widely studied. Received December 9, 1975; accepted for publication January 12, 1976. Supported in Part by Public Health Service Grant CA 17089-01 from the National Cancer Institute, and the Evelyn Steinberg Memorial Foundation, Chicago. Address reprint requests to Dr. Davidsohn: Department of Experimental Pathology, Mount Sinai Hospital Medical Center, California at loth St., Chicago, Illinois 60608. Dr. Lill's present address is: Basic Research, Frederick Cancer Research Center, Litton Bionetics, Inc., Frederick, Maryland. Dr. Norris is with the Armed Forces Institute of Pathology, Washington, D. C. Drs. Rubenstone and Chang-Lo are with the Department of Pathology and Dr. Davidsohn with the Department of Experimental Pathology, Mount Sinai Hospital Medical Center, Chicago, Illinois.
Studies by Christopherson and associates 1 indicate that eradication of dysplastic lesions would prevent the later development of invasive carcinoma. Richart and Barron 9 concluded that cervical neoplasia began as mild dysplasia and progressed to carcinoma in situ; however, the lesions were surgically removed at the carcinomain-situ stage so that no firm conclusion could be made as to their progression to invasive carcinoma. In their study only six of 463 women who had Class III Papanicolaou smears reverted to normal. In the remaining patients the cancers progressed to further classes or remained the same. Hall and Walton 6 reported that carcinoma in situ developed in 11.6% of a series of 206 women in whose cases the diagnosis of dysplasia had been made by biopsy, but 29.1% of those women had marked dysplasia. Green 5 reported that in a series of 142 patients who had basal-cell hyperactivity diagnosed by biopsy, 37% reverted
767
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Lill, Patsy H., Norris, Henry J., Rubenstone, Albert I., Chang-Lo, Mary, and Davidsohn, Israel: Isoantigens ABH in cervical intraepithelial neoplasia. Am J Clin Pathol 66: 767-774, 1976. T h e purpose of the study was to examine the relationship between the histologic findings and the presence or absence of ABH isoantigens in intraepithelial neoplasia of the cervix. After the lesions were graded by four pathologists, the Red Cell Adherence (RCA) test was done to demonstrate the ABH antigens, and the results of the two were compared. T h e correlation between the morphologic diagnosis and the results of the RCA test was limited. T h e percentages of tissues giving positive (+) or positive-negative (±) reactions were very similar in intraepithelial neoplasia (59.2%) and normal squamous epithelium (58.4%). T h e relationship of the RCA test results and behavior of the lesion was not studied. (Key words: Blood group antigens ABH; Cervix; Intraepithelial neoplasia; Immunopathology.)
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• "v -"••ivJ ' -.1 . !
a
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
af*'
V* FIG. 1 (upper). A (left). Hematoxylin and eosin. Normal squamous epithelium of the cervix. B (right). RCA test. The epithelium is RCA-positive, with the exception of the basal cell layer, a consistent finding. Blood group B. FIG. 2 (middle). A (left). Hematoxylin and eosin. Moderate intraepithelial neoplasia of the cervix (arrow) (morphologic score 10). B (right). RCA test. An example of a (±) reaction. Positive reaction seen in deep squamous epithelium (arrow), whereas the surface is negative. Blood group B. FIG. 3 (lower). A (left). Hematoxylin and eosin. Normal squamous epithelium of the cervix. B (right). RCA test. Positive reaction seen only in the deeper layers. Blood group A.
November 1976
ISOANTIGENS ABH IN NEOPLASIA
769
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
to normal. The disparity in results may be Table 1. Comparison of Morphologic explained by the biopsies removing the and RCA Scores lesions. Richart 8 reported that a biopsy Number of Palienis Who site that includes both normal and cervical Had RCA Score* intraepithelial neoplasia will tend to be Morphologic re-epithelialized by normal epithelium. Score I II III Petersen 7 reported that in a series of 127 12 7/16 4 5 women who had epithelial hyperplasia with 11 1/11 4 6 nuclear abnormalities and borderline cases 10 4/16 7 5 9 3/12 6 3 followed for as long as 15 years, invasive S 4/8 2 2 carcinoma developed in 34 (29.9%). 7 2/5 1 9 6 1/2 — 1 The Red Cell Adherence (RCA) test2-3 5 3/8 2 3 demonstrated that normal squamous epi4 1/4 2 1 thelium of the cervix contained ABH anti3 6/10 2 9 2 gens, but in 89 of 102 cases (87%) of in1 — — — vasive carcinoma the antigen was no longer 0 demonstrable in the cancer cells, and in (Normal) 15/36 6 15 11 of 102 (11%) the antigen was reduced Squamous metaplasia 5/16 5 6 in amount, as evidenced by patchy side-byTotal number of cases: 144 side positive and negative reactions. In two * 1. positive; 11. positive and negative; ill. negative. cases (2%) of invasive carcinoma, the RCA test was positive. T h e present study was undertaken in an attempt to correlate the was examined separately by four pamorphology and the presence or absence thologists (Robert J. Kurman, M.D., and of the ABH antigens in intraepithelial authors A.I.R., M.C.-L., and H.J.N.) and neoplasia of the cervix. scored on a scale of 0 (normal) to 3 (severe intraepithelial neoplasia). T h e individual Materials and Methods scores given by the four pathologists to each One hundred fifty-five examples of slide were totaled so that the final morphocervical lesions from the files of the AFIP logic scores for individual sections ranged were chosen to represent in approximately from 0 to 12. Squamous metaplasia was equal numbers normal tissue, squamous identified as such without a number score metaplasia, mild intraepithelial neoplasia, assigned. Eleven sections were eliminated moderate intraepithelial neoplasia, and from the study due to breakage (4), imsevere intraepithelial neoplasia. No proper fixation (1) and inadequate material attempt was made to differentiate severe left in the block (6). intraepithelial neoplasia from carcinoma in situ. The term "intraepithelial neoMorphologic Score plasia" is used as a generic term to designate all the potential precursors to inIt seemed logical that the morphologic vasive cancer, including mild, moderate score best reflected the degree of intraand severe dysplasia and carcinoma in situ. epithelial neoplasia using the following: Because of possible inconsistency among 0 Normal epithelium pathologists in their interpretations of the 3-6 Mild intraepithelial neoplasia atypicality in intraepithelial lesions, a score, 7-10 Moderate intraepithelial neorather than a diagnosis, was assigned each plasia slide. One representative block of each case Severe intraepithelial neoplasia was chosen. At least four sections were cut 11-12 (ca-in-situ) serially from each block. One hematoxylin and eosin-stained section from each block After a score was obtained, two partici-
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