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Expression of p63 in conjunctival intraepithelial neoplasia and
squamous cell carcinoma.Graefes
Arch Clin Exp Ophthalmol. 2006
Jan;244(1):96-103.
BACKGROUND:
p63 is a homologue of the tumour suppressor gene p53, which is
expressed in human basal squamous epithelium. Some investigators
maintain that p63 plays a role in the development of squamous
epithelium and, despite its homology to p53, it is considered to act
as an oncogene. This study investigated the expression of p63 in
conjunctival intraepithelial neoplasia of different grades, and
conjunctival squamous cell carcinoma and its correlation to the
proliferation marker MIB-1. MATERIAL AND METHODS: Seventeen
conjunctival specimens excised with the suspicion of either
conjunctival intraepithelial neoplasia (CIN) or squamous cell
carcinoma were diagnosed histologically as follows: 2 squamous cell
carcinomas of the conjunctiva, 2 CIN grade I, 3 CIN grade II, 7 CIN
grade III, 2 CIN with beginning invasion and 1 normal conjunctiva with
no dysplasia. Sixteen microscopically-normal postmortem conjunctival
specimens and normal conjunctiva, CIN and carcinoma specimens were
stained immunohistochemically with antibodies against p63 and MIB-1.
At least 500 cells per specimen were counted and the percentage of
positively-stained cells of each antibody was calculated. RESULTS: A
mean of 80% (57-89%) of the dysplastic cells from the CIN specimens
stained positively with antibodies against p63, especially in the
lower two-thirds of the epithelium, statistically significantly more
compared with the normal specimens (9-55%, mean 36%, p<0.001).
Nevertheless, we did not find a correlation between the percentage of
p63-positive cells and the differentiation grade of the malignant
specimens. MIB-1 positivity was shown by 0-1% of the cells in the
normal postmortem controls, by 3-30% (mean 12%) of the cells in the
basal and occasionally in the middle layer of the CIN specimens, and
16-61% (mean 23%) in the carcinoma specimens. CONCLUSION: In
conjunctival intraepithelial neoplasia and squamous cell carcinoma of
the conjunctiva, p63 is preferentially expressed in the immature
dysplastic epithelial cells. Its staining does not correlate with
MIB-1-expression, and therefore does not appear to be linked to cell
proliferation.
HLA class
II antigen expression in conjunctival precancerous lesions and
squamous cell carcinomas.Curr
Eye Res. 2003 Sep;27(3):151-5
PURPOSE: The
expression of human leukocyte antigen (HLA) class II molecules on the
cell surface is necessary for the presentation of peptide antigens to
helper CD4 T lymphocytes of the immune system. We studied the
immunoexpression of HLA class II antigen in conjunctival precursor
lesions and conjunctival squamous cell carcinomas. METHODS: HLA class
II antigen expression was analyzed in 8 conjunctival dysplasias, 6
carcinomas in situ and in 7 conjunctival squamous cell carcinomas, by
immunoperoxidase staining with monoclonal antibody to HLA class II
antigen on the archival clinical samples. Immunoanalysis was done by a
semi quantitative method based on the intensity of staining and the
percentage of stained cells. RESULTS: HLA class II antigen
immunoexpression was heterogeneous in 8 conjunctival dysplasias and in
6 carcinoma in situ and negative in 7 conjunctival squamous cell
carcinomas. CONCLUSIONS: Human leukocyte class II antigen
immunoexpression is decreased in conjunctival precancerous and
squamous cell carcinomas.
High-frequency
ultrasonographic evaluation of conjunctival intraepithelial neoplasia
and squamous cell carcinoma.Arch
Ophthalmol. 2003 Feb;121(2):168-72.
OBJECTIVE: To
evaluate the high-frequency B-scan ultrasonographic characteristics of
squamous conjunctival neoplasia (conjunctival intraepithelial
neoplasia and squamous cell carcinoma). METHODS: Each of 11 patients
was examined with 20- and/or 50-MHz ultrasonography in a retrospective
consecutive case series. MAIN OUTCOME MEASURES: Ultrasonographic
findings with clinical and histopathologic correlations. RESULTS:
Eleven eyes of 11 patients (8 men) were affected. Disease involved the
right eye in 6 (55%) of the patients and the left eye in 5 (45%) of
the patients; it was multifocal in 5 (45%) of the eyes. All tumors
extended to, or primarily involved, the limbal conjunctiva. One
patient developed superficial spread overlying a functioning
partial-thickness filtering bleb, 1 developed intraocular extension, 1
developed scleral invasion, and 3 developed orbital involvement before
treatment. Results of ultrasonographic examinations showed that the
superficial aspect of the smaller limbal tumors appeared as fusiform
thickening of the conjunctiva. In all patients, the tumor surface was
highly reflective in contrast to the characteristically low
reflectivity seen within the tumor stroma. Intraocular tumor extension
was variably reflective, but evidenced by blunting of the anterior
chamber angle and thickening of the uvea. Orbital extension was viewed
as low reflective tumor extension into the relatively hyperechoic
orbital tissues. CONCLUSIONS: High-frequency ultrasonography may be
used to assess the extent of squamous conjunctival neoplasia. While
the 50-MHz system offered better resolution, 20-MHz ultrasonography
allowed for a wider and deeper field of view. High-frequency
ultrasonography was useful in determining tumor thickness, shape, and
internal reflectivity, and especially in revealing tumor extension
into the sclera, eye, and orbit.
Human
papillomavirus 16 and 18 expression in conjunctival intraepithelial
neoplasia.Ophthalmology.
2002 Mar;109(3):542-7.
OBJECTIVE: To
evaluate conjunctival intraepithelial neoplasia (CIN) and normal
conjunctiva for the presence of human papillomavirus (HPV) DNA and for
expression (as detected by the presence of mRNA) of the HPV E6 region.
DESIGN: Prospective, case-controlled study. PARTICIPANTS: Ten
consecutive patients who underwent CIN excision by one surgeon (CLK)
and five age-matched control subjects who underwent retinal detachment
repair at the Bascom Palmer Eye Institute. METHODS: A reverse
transcriptase in situ polymerase chain reaction (PCR) technique was
used to search for the presence of HPV mRNA in CIN specimens from 10
consecutive patients who underwent CIN excision by one surgeon (CLK)
at Bascom Palmer Eye Institute, as well as in clinically uninvolved
conjunctival specimens from the same eyes of these patients. In
addition, conjunctival specimens from five control subjects
(age-matched to five of the cases), who had no clinically identifiable
conjunctival disease and who underwent retinal detachment repair at
the Bascom Palmer Eye Institute, were analyzed in a similar manner.
The clinical diagnoses of CIN and normal conjunctiva were confirmed
histopathologically in all cases by an ocular pathologist, who was
masked as to the patients' clinical diagnoses, and the PCR testing was
performed by an investigator (GJN) who was masked as to the clinical
diagnoses. RESULTS: HPV 16 DNA and mRNA were present in five CIN
specimens, and HPV 18 DNA and mRNA were present in the other five CIN
specimens; neither HPV 16 or 18 DNA nor mRNA were detected in any of
the control specimens or in any of the clinically uninvolved
conjunctival specimens (P < 0.001). In each of the CIN specimens, 20%
to 40% of the dysplastic cells expressed the HPV E6 region.
CONCLUSIONS: HPV 16 or 18 DNA and mRNA corresponding to the E6 region
were detected in all CIN specimens examined. HPV 16 or 18 DNA or mRNA
was not present in any of the control or uninvolved conjunctival
specimens. The consistency of the current findings with those reported
for human cervical malignant lesions, and the fact that the protein
encoded by the E6 region of HPV 16 and 18 has been shown to form a
complex with the protein encoded by the host tumor suppressor gene
p53, provide strong evidence for an etiologic role of HPV in the
development of CIN.
Possible
prognostic markers in conjunctival dysplasia and squamous cell
carcinoma.Jpn
J Ophthalmol. 1998 Jul-Aug;42(4):256-61.
Conjunctival
squamous cell carcinoma (SCC) can develop from carcinoma in situ or
severe dysplasia known as conjunctival intraepithelial neoplasia (CIN).
Conjunctival intraepithelial neoplasia and SCC are histopathologically
well-defined conditions. However, it is difficult to determine the
grading of dysplasia by clinical morphologic findings. Recently,
proliferating cell nuclear antigen (PCNA) immunostaining, p53
immunostaining, and argyrophilic nucleolar organizer regions (AgNORs)
staining have been established as valuable means of studying the
biologic behavior of malignant cells. In the present study, these
three staining techniques were used to examine histologic preparations
of three conjunctival dysplasia and one SCC lesion. Five conjunctival
tumor samples were obtained from four patients between July 1993 and
October 1995. Following formalin fixation and embedding in paraffin,
PCNA, and p53 immunostaining and AgNORs staining was performed with
all tissue specimens. The PCNA-positive rate was the highest in SCC,
followed by severe dysplasia and mild dysplasia. The p53-positive rate
was the highest in severe dysplasia, followed by mild dysplasia, and
negative in SCC. The AgNORs-count increased as malignancy advanced.
These staining methods, which are markers for proliferative potency
and cell differentiation, will be useful for early detection of
changes in malignancy and will aid in decisions on treatment and
prognosis.
Detection of
human papillomavirus infection in squamous tumours of the conjunctiva
and lacrimal sac by immunohistochemistry, in situ hybridisation, and
polymerase chain reaction.Br
J Ophthalmol. 1997 Apr;81(4):308-13.
BACKGROUND:
Squamous tumours of the ocular surface, including the lacrimal
pathway, range from benign lesions to invasive carcinomas. Some of
these tumours are associated with human papillomavirus (HPV)
infection, with the types of HPV differing among papillomas and
dysplastic or malignant lesions. METHODS: The relation between
squamous tumours of the conjunctiva and lacrimal sac and HPV infection
was investigated in 17 individuals with such tumours. Nine of the 17
tumours were benign, four were dysplastic lesions, and four were
carcinomas. RESULTS: Eight specimens showed positive
immunohistochemical staining with antibodies to HPV; four of these
eight were papillomas, three were dysplastic lesions, and one was a
carcinoma. Koilocytosis was detected in seven of these eight tumours.
Five of the eight specimens positive for immunohistochemical staining
were also positive for HPV DNA by in situ hybridisation, and all eight
were positive for HPV DNA by the polymerase chain reaction (PCR)
method. CONCLUSION: Approximately 50% of squamous tumours of the
ocular surface and lacrimal sac were associated with HPV infection.
This is the first report, to our knowledge, of the detection of HPV in
the field of ophthalmology by a combination of immunohistochemistry,
in situ hybridisation, and PCR.
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