Major histocompatibility complex class II polymorphisms and risk of cervical cancer in Puerto Rican women

Association between HLA antigens and cervical squamous cell carcinoma has been described in several populations. To verify whether HLA-DRB1 and DQB1 diversity is related to cervical cancer in Puerto Rican women, 40 cases and 50 controls were HLA typed. DRB1*16 (POR=2.89) and DRB1*11 (POR=1.74) were positively associated with cervical cancer. A negative association was found with DRB1*01 (POR=0.52), DRB1*04 (POR=0.60), DRB1*14 (POR=0.33), DRB1*15 (POR=0.65), DQB1*04 (POR=0.33), DQB1*05 (POR=0.64) and DQB1*06 (POR=0.65). We suggest that HLA Class H polymorphisms are involved in genetic susceptibility to cervical cancer in Puerto Rican women. These results should be confirmed in studies with larger sample size to preclude the possibility of false positive observations.

Comparison of the endocervical brush and the endocervical curettage for the evaluation of the endocervical canal.

OBJECTIVE: To evaluate and compare the efficacy in obtaining an adequate endocervical sampling using the endocervical brush and the endocervical curettage. METHODS: Analysis of the cytology and histology of samples obtained from patients referred to the University of Puerto Rico School of Medicine Tertiary Care Center Anaplasia Clinics for colposcopy due to an abnormal Pap smear having atypical cells or higher as classified according to the Bethesda System. All patients underwent evaluation of the endocervical canal with an endocervical brush and an endocervical curettage. RESULTS: Fifty three of fifty-eight patients had correlating endocervical brush Papanicolaou smear and endocervical curettage. Only five patients presented discrepancies. All endocervical brush samples had sufficient tissue for diagnosis. CONCLUSION: The endocervical curettage is operator dependent, is difficult to perform in patients with a stenotic cervical os or in menopausal patients. The endocervical brush is easier to use, malleable and has a lower processing cost. In view of these findings evaluation of the endocervix can be safely performed with the use of an endocervical brush. When used properly, the endocervical brush has a sensitivity of 90%, a specificity of 92.1% and a positive predictive value of 87.5%.

Histologic characterization of uterine papillary serous adenocarcinoma.

Uterine papillary serous adenocarcinoma (UPSC) is one of the most aggressive endometrial tumors. UPSC has been associated with an increased propensity for extrauterine spread. Survival rates of not more than 50% are commonly reported even for tumors which appear to be confined to the uterus. Small areas of UPSC can be found in otherwise well-differentiated endometrial lesions and yet still determine the overall prognosis. In the present study we evaluated histologic criteria that might be helpful in diagnosing small-volume UPSC, including silver-stained nucleolar organizer regions (AgNOR) which have prognostic importance in a variety of tumors, and nuclear size which has been used for prognostication in endometrial cancer. We examined 25 UPSC specimens and compared them to grade III (GIII, n = 10) and grade I (GI, n = 10) typical endometrial adenocarcinoma using the following parameters: mean AgNOR count per cell was UPSC 6, GIII 6.0, and GI 4.3; mean AgNOR area was UPSC 1.28 microns2, GIII 1.35 microns2, and GI 0.86 microns2; total AgNOR area per cell was UPSC 7.5 microns2, GIII 8.13 microns2, GI 4.47 microns2; and nuclear size was UPSC 66.9 microns2, GIII 60.3 microns2, GI 34.8 microns2. All differences between UPSC or GIII tumors and GI lesions were statistically significant. Overexpression of p53, as determined histochemically, was seen in 64% of the UPSC specimens. UPSC is characterized by high AgNOR count and area per cell, large nuclear size, and a high rate of p53 overexpression. Evaluation of these parameters in biopsy material may aid in selecting high-risk patients for adjuvant therapy trials.

Immunocytochemical analysis of uterine papillary serous carcinomas for estrogen and progesterone receptors.

Uterine papillary serous carcinoma (UPSC), an aggressive histologic variant of endometrial cancer, is particularly resistant to cytotoxic chemotherapy. In reviewing a group of patients treated with cisplatin, doxorubicin, and cyclophosphamide, we were surprised to find that 90% of specimens tested by biochemical analysis were positive for estrogen receptor (ER), progesterone receptor (PR), or both. To further study receptor content and localization, we performed immunocytochemical analysis (ICA) on 29 archival UPSC specimens. In ER studies, three specimens were unevaluable because of inadequate internal controls; of the remaining 26, only two were ER positive, showing weak, focal staining. In PR studies, 18 samples had adequate controls, and all tumor specimens were receptor negative. Corresponding biochemical ER data were available for 11 cases, of which 10 were ER positive. ICA, however, showed all 10 to be negative. Biochemical PR data were available for seven samples: Six were positive. All six biochemically positive PR specimens were PR negative when analyzed by ICA. Biochemical assays for ER and PR may overestimate positivity as a result of contamination with normal tissue or the presence of receptor-positive typical endometrial adenocarcinoma in tumors of mixed histology. ICA may eliminate this problem, but it has technical limitations, especially when used for archival tissue analysis. Because urinary papillary serous carcinoma appears to be a receptor-negative tumor, further evaluation of hormonal therapy is not likely to be beneficial.

Human papillomavirus DNA in tissue biopsy specimens of vulvar vestibulitis patients treated with interferon.

Thirteen women with the diagnosis of vulvar vestibulitis based on clinical symptoms, presence of vestibular tenderness on physical examination, and acetowhite changes of the vulvar vestibule were treated with intradermal injection of alpha-interferon. Biopsies of the acetowhite areas were analyzed for human papillomavirus (HPV) DNA using polymerase chain reaction amplification and dot blot hybridization. Eleven of 13 subjects harbored one of the HPV DNA types; six of these were type 16 and/or 18 and the others were unidentified. Five subjects (all HPV DNA-positive) reported resolution of symptoms with interferon therapy. Our results indicate the presence of HPV DNA in a subset of patients with vulvar vestibulitis, but its presence is not predictive of response to interferon therapy.

Cross-reactivity of monoclonal antibodies directed against lymphocyte markers with trophoblast cells of normal placenta, hydatidiform mole, and gestational choriocarcinoma.

The current study was undertaken to characterize the expression of trophoblast-lymphocyte cross-reactive antigens on normal, molar, and malignant trophoblast. A panel of monoclonal antibodies directed against lymphoid cell markers were tested in immunofluorescence assay on cryostat sections of placenta and mole and on monolayers of choriocarcinoma cells. NKH-1, a monoclonal antibody to natural killer cells, reacted with both molar and placental villous trophoblast and with two choriocarcinoma cell lines. NKH-2, a monoclonal antibody reactive with a subset of natural killer cells, did not react with placental villous trophoblast but reacted with molar villous trophoblast in three of five moles tested and with both choriocarcinoma cell lines. B5, a monoclonal antibody which reacts with activated B cells, reacted with both choriocarcinoma cell lines but did not react with normal placental or molar trophoblast. MY7, a monoclonal antibody to myeloid colony-forming cells, reacted with only one of the choriocarcinoma cell lines. Trophoblast-lymphocyte cross-reactive antigens may be important in the immunobiology of gestational trophoblastic disease by modulating interactions between the trophoblast and the maternal immune system.

Expression of trophoblast-leukocyte common antigens and placental-type alkaline phosphatase in complete molar pregnancy.

The current study was undertaken to determine the localization of trophoblast-leukocyte common antigens and placental-type alkaline phosphatase in complete molar pregnancy with the use of rabbit antiserum and murine monoclonal antibodies in immunofluorescence assays. Trophoblast-leukocyte common antigens were expressed on all normal villous trophoblast (8 to 38 weeks' gestation) and on all complete moles studied. Placental-type alkaline phosphatase was not expressed on villous trophoblast before 20 weeks' gestation in either normal placentas or complete moles. In contrast, there was strong expression of placental-type alkaline phosphatase on villous trophoblast of normal placentas of more than 20 weeks' gestational age. The expression of polymorphic antigens such as trophoblast-leukocyte common antigens and placental-type alkaline phosphatase on molar trophoblast may be important in the immunobiologic features of gestational trophoblastic disease.

Immunobiology of complete molar pregnancy and gestational trophoblastic tumor.

The unique curability of gestational trophoblastic tumors may in part be attributable to a host immunologic response. The occurrence of rapidly progressive and fatal choriocarcinoma may be favored by histocompatibility between patients and their partners. However, histocompatibility is not a prerequisite for the development and persistence of gestational choriocarcinoma. The expression of HLA by choriocarcinoma cells in culture is enhanced following incubation with gamma-interferon and this may be of both biologic and clinical significance. Complete molar pregnancy is a complete allograft because all molar chromosomes are of paternal origin. Patients with complete mole are sensitized to paternal HLA antigen which is expressed in molar tissue. Other polymorphic antigen systems including trophoblast-leukocyte common antigens and placental-type alkaline phosphatase are also expressed in molar tissue. We have studied the immunopathology of the molar implantation site to investigate possible humoral and cellular immune responses. The relationships among normal placenta, complete mole and choriocarcinoma are not clearly understood. The pattern of expression of oncofetal antigens in these three gestational tissues may be used to assess trophoblastic differentiation. In studies to date, molar trophoblast has the same pattern of expression of oncofetal antigens as normal placental trophoblast. We will review recent advances in our understanding of the immunobiology of gestational trophoblastic disease and suggest new directions for further research.