In favor of annual screening for cancer of the cervix uteri

A case of polymyalgia rheumatica with atypical manifestations, including carpal tunnel syndrome, distal myalgias and a low eritro sedimentation is reported. The association of polymyalgia rheumatica and carpal tunnel syndrome is controversial. Although it has been reported previously in a recent and large review of carpal tunnel syndrome in Rochester, USA, there was not any more cases of polymyalgia rheumatica associated with carpal tunnel syndrome than in the general population. In our patient, the symptoms of polymyalgia rheumatica and of carpal tunnel syndrome were present at the beginning, and both responded satisfactorally to the treatment with methylprednisone. This form of presentation and its response to treatment suggest that the symptoms of carpal tunnel syndrome are caused by the inflammation of the carpal synovial, which is an unfrequent manifestation of polymyalgia rheumatica. We report this case for the purpose of altering to an unusual form of presentation of polymyalgia rheumatica in order to avoid unnecessary surgery for the carpal tunnel syndrome.     

Differential expression of telomerase activity in human cervical cancer and cervical intraepithelial neoplasia lesions

PURPOSE: Telomeres are tandem arrays of repeated DNA sequences located at the ends of eukaryotic chromosomes, and are synthesized by the enzyme telomerase. Loss of telomeric DNA may play an important role in the development of human cancers. However, very little is known about the status of telomerase during human cervical cancer development. PATIENTS AND METHODS: Telomerase activity was measured by telomere repeat amplification protocol (TRAP) assay in 24 cervical cancers, one carcinoma in situ (CIS), and 20 cervical intraepithelial neoplasia (CIN) lesions. Adjacent nontumor cervical tissue from the same 24 cervical cancer patients and normal cervical tissues from 11 control individuals also were examined for the presence of telomerase activity. RESULTS: Twenty two of the 24 (91.7%) cervical cancer specimens and the single CIS tissue were strongly positive for telomerase activity. Relatively weak but distinctive telomerase activity also was detectable in one of four CIN-I (25%), two of eight CIN-II (25%), and two of eight CIN-III (25%), respectively. However, telomerase activity was not found in the 24 corresponding nontumor cervical tissues from the same cervical cancer patients and the 11 normal cervical tissues from control individuals. CONCLUSION: The majority of cervical cancers contain strong telomerase activity. Significant proportions of noncancerous CIN tissues also contain telomerase activity, although weaker than that in cervical cancer. It seems that there is a progressive increase of telomerase activity in association with an increased degree of cervical malignancy. These results seem to suggest that the expression of telomerase may play a crucial role in cervical cancer carcinogenesis.     

Virological and biological characteristics of cervical intraepithelial neoplasia grade I with marked koilocytotic atypia

The aim of this study was to evaluate virologic and biological significance of marked koilocytotic atypia observed in some cases of grade I cervical intraepithelial neoplasia (CIN I). Thirty-one CIN I cervical biopsy specimens with marked koilocytotic atypia, defined by the presence of meganuclei in the superficial epithelial layers, were compared to 37 CIN I biopsy specimens with usual koilocytes for (1) the human papillomavirus (HPV) type and signal pattern as detected by nonisotopic in situ hybridization (ISH); (2) the proliferation index assessed by Ki 67 immunostaining and (3) the p53 labeling pattern. Interobserver agreement for meganuclei was excellent (k = 0.9). Twenty-five out of 68 biopsies (37%) were positive by ISH for the 6 of 11 HPV probe, 30 (44%) for the 16-18 probe, and 7 (10%) for the 31/33 HPV probe, 6 (9%) were negative for ISH. The presence of meganuclei was strongly related to high and intermediate risk HPV type (P = 0.0001). The sensitivity and specificity of meganuclei for the detection of high or intermediate risk HPV in CINI were 73 and 87%, respectively. Loss of p53 immunostaining in the lower third of the epithelium was also related to the presence of meganuclei (P < .05), but the MIB-1 index and ISH labeling pattern were not. In conclusion, marked koilocytotic atypia in CIN I is a reliable and sensitive marker for infection by high or intermediate-risk HPV, and might be a guide to therapy.     

Colposcopy and the management of cervical intraepithelial neoplasia

The stable, bound iodine in the thyroid colloid of Triturus helveticus has been studied with the electron microprobe. Some animals show a normal development. Others are accidentally neotenic due to certain ecological conditions. The values of punctate iodine concentrations (CPI) have been computed and expressed in relative units (counts/s). The mean CPI per lumen is very variable from one follicle to another in the same thyroid section. During normal development, the mean CPI per animal is generally higher in metamorphosing individuals than in larvae. During development with neoteny, the mean CPI per animal attains high values if the larval state is maintained in its totality; the CPI decreases in partially metamorphosed animals, but increases again after metamorphosis. The amount of halogen contained in the thyroid colloid has been computed in relative units (colloid iodine pool). Throughout normal development, the pool remains small if the animals have not attained the adult state. In increases considerably in entirely larval neotenic newts, decreases during metamorphosis but increases afterwards. In totally neotenic newts, the thyroid gland receives only a low hypophyseal stimulation and reacts as the thyroid gland of various hypophysectomized Urodeles. Our results pose the problem as to whether TSH regulates the transepithelial iodine flows, which permit the expansion of the colloid iodine pool, when this hormone is secreted at a very low levels.     

Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia

BACKGROUND: Epidemiologic studies have demonstrated strong and consistent associations between the detection of human papillomavirus (HPV) type 16 DNA and the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, HPV16 is also the most common type of HPV in the normal population, and only a minority of women with HPV16 infection develop cervical cancer. Studies of genomic heterogeneity in HPV16 have demonstrated the presence of multiple variant forms in all human populations examined to date. It is conceivable that the natural variants of HPV16 in a given population may not have the same biologic behavior. PURPOSE: This study was designed to determine the association between natural variants of HPV16 and the risk of biopsy-confirmed CIN 2 or 3, the most important precancerous lesions of the uterine cervix. METHODS: Prospective studies were conducted among 1) women attending a university and 2) women presenting to a sexually transmitted disease clinic. Subjects were eligible for inclusion in this investigation if the initial cytologic findings did not reveal CIN 2-3 and HPV16 DNA was detected by means of a polymerase chain reaction (PCR)-based method in one or more cervical or vulvovaginal samples. Eligible subjects were followed every 4 months with cervical Pap smears and colposcopic examinations. Women were referred for biopsy if cytology or colposcopy suggested CIN 2-3. Two groups of HPV16 variants, prototype-like and nonprototype-like, were determined by means of single-strand conformation polymorphism (SSCP) analysis of PCR products from the noncoding region of the viral genome. Representative SSCP patterns from HPV16 variants were further characterized by direct DNA sequencing of the PCR products. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox regression analysis. RESULTS: Prototype-like variants accounted for 79% of the HPV16 detected in university students and 86% of the virus detected in patients presenting to the sexually transmitted disease clinic. CIN 2-3 was confirmed by biopsy in nine of 57 HPV16-positive women attending the university and in 10 of 66 HPV16-positive women presenting to the sexually transmitted disease clinic. Among university students, those with HPV16 nonprototype-like variants were 6.5 (95% CI = 1.6-27.2) times more likely to develop CIN 2-3 than those with prototype-like variants. A similar association was observed among women presenting to the sexually transmitted disease clinic (RR = 4.5; 95% CI = 0.9-23.8). CONCLUSIONS: This study suggests that the risk of developing CIN 2-3 is not the same with all variants of HPV16 and that nonprototype-like variants confer a greater risk compared with prototype-like variants. The important genomic differences underlying this increased risk of CIN 2-3 remain to be determined.     

Frequency of cervical intraepithelial neoplasia following large loop excision of the transformation zone

Acute ophthalmoparesis (AO) is a monophasic disease characterized by acute onset of paresis of the extraocular muscles without ataxia or areflexia. Here we report a case of AO with gadolinium enhancement in the cisternal portion of the abducens nerves using contrast-enhanced three-dimensional magnetic resonance imaging.     

Authors' experience in the treatment of cervical intraepithelial neoplasia

BACKGROUND: During the last ten years, after the destroying intervention for the treatment of cervical intraepithelial uterine neoplasia (CIN = Cervical Intraepithelial Neoplasia) was abandoned, space has been given to the conservative treatment, both destructive and excisional. In this study, conducted at the Department of Gynaecology and Obstetrics of Eboli Hospital (ASL Salerno 2) in collaboration with the Gynaecological and Obstetrical Department of the Second University of Naples, the authors compared the various therapy techniques of the conservative excisional type, using 5 different methods. METHODS: One hundred and fifty-seven women, all with lesions of the neck of the uterus of varying degrees of severity, underwent the treatment. Cytologic and colposcopical controls (follow-up) were carried out at intervals over a period of time. RESULTS: In 5 of the 95 patients (5.3%) who underwent surgical conisation, the presence of invading carcinoma was noted. Of the 19 women treated with diathermical loop, 3 cases of mature squamous metaplasia, 3 cases of CIN I, 8 cases of CIN II, and 4 cases of CIN III were observed. In the 32 patients treated with laser-therapy a complete recovery, equal to 100% was obtained although with slight margins of under-estimation and over-estimation; the same result was verified in the 3 patients treated with electroresection with high frequency radio waves and in the 8 patients treated with microneedle. CONCLUSIONS: On the basis of these results it is concluded that lasertherapy and electroresection with high frequency radio waves (3.8 MHz) using electrodes with "bands" or with "linears" (microneedle) gave the best results for both the therapeutical advantages with anatomical and functional integrity of the cervix and for economic reasons.     

Vaginal intraepithelial neoplasia (VAIN) following hysterectomy in patients treated for carcinoma in situ of the cervix

BACKGROUND: Cell adhesion in the limbal region is of outstanding importance for the regeneration of the corneal epithelium and for repair mechanisms after antiglaucomatous fistulating surgery. In the basement membranes cell adhesion is largely modified by the extracellular matrix protein laminin. The aim of our study was to establish the immunohistochemical pattern of the different laminin-isoforms and subunits in the basal membrane of the limbal conjunctiva and episcleral vessels. MATERIAL AND METHOD: For immunohistochemistry five normal human donor eyes were included; we used antibodies against the laminin heterotrimers 1 and 2, against the laminin subunits alpha 2, beta 1, beta 2, gamma 1, gamma 2 and against the laminin-associated protein nidogen. RESULTS: The basement membrane of the limbal conjunctiva reveals immunoreactivity against all used antibodies. The subconjunctival and episcleral vessels showed no staining for the laminin subunit gamma 2, but for all other used antibodies. CONCLUSION: The basement membrane of the limbal and conjunctival epithelium as well as the basement membrane of subconjunctival and episcleral vessels express a broad spectrum of laminin variants. This diversity emphasizes functional specialization of the limbal region, although the exact importance of the laminin variants is still unknown.     

The roles of the human major histocompatibility complex and human papillomavirus infection in cervical intraepithelial neoplasia and cervical cancer

Germ theory and pure culture methods have provided invaluable information concerning the role of bacteria in diseases resulting from a single organism which bypasses a host's defenses. However, they do not provide sufficient information concerning the synergisms which allow the members of biofilm communities to proliferate more effectively as communities rather than as individuals. The mechanisms of these synergies are potential targets for antimicrobial agents as well as potential mechanisms of resistance to antimicrobial agents. Understanding community-level phenomena in oral biology requires the culture, identification, and classification of functional plaque communities as well as new methods of identifying and quantifying communal relationships. Cultured biofilm communities also provide ideal models of bacterial self-organization in which information related to adaptive strategies arises not only through the recombination of genes within genomes, but also through the recombination of organisms within communities.     

Epithelial changes in the cervix uteri in pregnant women and in cervical oncogenesis

The changes in the growth and differentiation of the cervical epithelium induced during pregnancy by hormonal influence and anatomical alterations are discussed regarding their magnitude on cervical oncogenesis. Question about the necessity of the self-sufficient centralized reporting of the pregnant women with precancer and cancer lesions is put on.     

High-dose-rate intracavitary brachytherapy in the management of cervical and vaginal intraepithelial neoplasia

PURPOSE: To assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with grade 3 cervical intraepithelial neoplasia (CIN-3) and grade 3 vaginal intraepithelial neoplasia (VAIN-3). METHODS AND MATERIALS: This was a retrospective analysis in 20 patients with CIN-3 (n = 14) or VAIN-3 (n = 6), average age 61.9 years, managed with HDR-ICR at Kanagawa Cancer Center. Two patients with CIN-3 with microinvasive foci and 11 other patients with CIN-3 were treated with HDR-ICR for cervical lesions. Six patients with CIN-3 after hysterectomy received HDR-ICR for recurrent or residual VAIN-3 lesions. One patient received radiation therapy for both CIN-3 and VAIN-3 lesions. All these patients but one were postmenopausal. RESULTS: Seventeen patients were treated with HDR-ICR alone, and three with combined external radiation therapy. The dose was calculated at Point A located 2 cm superior to the external os and 2 cm lateral to the axis of the intrauterine tube for intact uterus. For lesions of the vaginal stump, the dose was calculated at a point 1 cm superior to the vaginal apex or 1 cm beyond vaginal mucosa. In the 14 patients treated for CIN-3 lesions, the mean total dose of HDR-ICR was 26.1 Gy (range 20-30). Six patients received HDR-ICR for VAIN-3 lesions with mean dose of 23.3 Gy (range 15-30). At follow-up (mean 90.5 months; range 13-153), 14 patients were alive and 6 had died owing to nonmalignant intercurrent disease. No patient developed recurrent disease. Rectal bleeding occurred in three patients, but this symptom subsided spontaneously. Moderate and severe vaginal reactions were noted in two patients, in whom the treatment had included the entire vagina. CONCLUSIONS: HDR-ICR can be employed as the primary management strategy for postmenopausal women with CIN-3. In intraepithelial neoplasia involving the vaginal wall after hysterectomy, HDR-ICR should be considered as an alternative to total vaginectomy.     

Immunohistochemical overexpression of p16 protein associated with intact retinoblastoma protein expression in cervical cancer and cervical intraepithelial neoplasia

A 35-year-old man with non-Hodgkin's lymphoma (NHL) (follicular small cleaved, B cell, stage IVB) received double myeloablative chemotherapy with syngeneic peripheral blood stem cell transplantation (PBSCT). Although platelet recovery was delayed until day 29 after the second transplantation, thereafter trilineage hematopoietic reconstitution was achieved. The evaluation after PBSCT did not detect any residual tumor. The patient was in good health until day 138, when his platelet count suddenly began falling; on day 150, it had fallen to 1.5 x 10(4)/microliter, and the patient was re-admitted for treatment. The bone marrow was normocellular with a normal count and megakaryocyte structure. Other examinations, including serological tests and computed tomography of the neck, chest, abdomen, and retroperitoneum, did not indicate a recurrence of NHL or reveal the cause of thrombocytopenia. The patient's platelet-associated IgG (PAIgG) level was at 70.9 ng/10(7) platelets (normal range: 9-25 ng/10(7) platelets); a diagnosis of thrombocytopenia due to an autoimmune mechanism such as idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone therapy increased the platelet count and reduced the PAIgG level. Thrombocytopenia with an ITP-like mechanism rarely occurs more than 100 days after autologous or syngeneic stem cell transplantation, and should be taken into consideration as a late complication of PBSCT.     

Expression of CD44 and variant isoforms in cervical intraepithelial neoplasia

The cell adhesion molecule CD44 and its variant isoforms have been found to be related to invasive and metastatic character of cancer cells. Their expression in gynecologic precancerous lesions has not yet been reported. Mouse monoclonal antibodies directed against a common epitope (CD44s) and exons 4v, 6v, and 9v were used to study the expression of CD44 and variant isoforms by immunohistochemistry in cervical intraepithelial neoplasia (CIN). Twenty tissue samples with normal cervical epithelium and 57 samples with CIN of different histological grades and different HPV status were included in this study. The standard CD44, CD44-4v, CD44-6v, and CD44-9v were expressed in normal cervical epithelium and in precancerous lesions. In distinct contrast to the normal epithelium, however, the standard CD44, CD44-4v, and 6v showed a reduced expression in precancerous lesions, whereas CD44-9v was significantly overexpressed. Expression of CD44 standard and CD44-4v was correlated with the histological grade but not with the HPV status. Compared with mild and moderate dysplasia, severe dysplasia and carcinoma in situ are associated with low expression of CD44s (P = 0.007) and of CD44-4v (P = 0.03). These observations reveal dynamic changes in CD44 expression during neoplastic cell transformation in cervical intraepithelial neoplasia.     

Human papillomavirus investigation of patients with cervical intraepithelial neoplasia 3, some of whom progressed to invasive cancer

Unstable expansion of the CTG repeats in the 3' untranslated region encoding a member of the protein kinase family in the q13.3 band on chromosome 19 is a mutation specific for myotonic dystrophy. To examine the correlation between clinical expression and CTG trinucleotide repeat length, we carried out Southern blot analysis in a family with myotonic dystrophy. In this pedigree, the expanded CTG repeats were transmitted maternally. The mother had three female children. The mother had about 200 CTG repeats, and the number of repeats for each child was about 800, 1500 and 1600 in birth order. The mother and the patient with 800 repeats were unaware of muscle weakness or myotonia. Symptoms were present from age 3 years in the patient with 1500 repeats and from birth in the one with 1600 repeats. Although the mother menstruated regularly, the patients with 800 and 1500 repeats both menstruated irregularly, and the one with 1600 repeats has never menstruated. The age of onset and severity of the disease were correlated with the size of the expanded repeats. Endocrinological studies revealed that the basal levels of the gonadotropins, PRL and E2 were within normal range, and a pituitary response to LHRH was observed. These data suggest that the amenorrhea and menstrual irregularities were caused by a suprahypophyseal dysfunction. When expanded CTG repeats are transmitted maternally, abnormal products resulting from the metabolic disturbance in the affected mother may harm the fetus in utero. A heterozygous fetus, who has more CTG repeats, may be unable to metabolize the pathologic products sufficiently and therefore may become more severely affected. This may explain the exclusive maternal transmission of congenital myotonic dystrophy.     

The frequency of Chlamydia trachomatis infection in women with intraepithelial neoplasia of the uterine cervix

A case of a rare form of Sanfilippo disease, mucopolysaccharidosis type III D is presented. The cause of the disease is a deficit of N-acetylglycosamine-6-sulfate sulfatase. Differences in clinical course and symptoms with type A and B Sanfilippo disease are shown (later presentation of symptoms, milder course, lack of distinct psychomotor regression and differences in characteristic phenotypic traits, such as facial features, joint contracture, tall height). It is suggested that type III D mucopolysaccharidosis be taken into account in the differentiation of mental retardation syndromes with hyperactivity.     

A multicentre study comparing cervicography and cytology in the detection of cervical intraepithelial neoplasia

The efficacy of local delivery of recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) to promote bone regeneration, with or without cellular contribution from the periosteum, was evaluated in transosseous defects. Implantation of rhTGF-beta 1 into 5 mm in diameter "critical size defects" in the rat mandible resulted in a dose-dependent (0.1-20 micrograms/defect) bone bridging at both 12 and 24 days, independent of the type of delivery system [3% methyl cellulose gel, porous CaCO3 particles, or poly(lactide-co-glycolide) beads]. The bridging, however, never exceeded 24% at 12 days or 34% after 24 days. In contrast, when access of cells from the periosteum to the defect was prevented by means of microporous expanded polytetrafluoroethylene barrier membranes (GORE-TEX membrane), rhTGF-beta 1 caused a dose-dependent inhibition of bone regeneration. The bioactivity of the growth factor was confirmed by implantation of 5 or 10 micrograms rhTGF-beta 1 in 12 mm in diameter bicortical defects in rabbit calvaria, which resulted in complete bone healing within 28 days, whereas control defects displayed a bridging of 40%-50%. The findings support the concept, based on in vitro experiments by others, that TGF-beta 1 primarily has a proliferative effect on cells already committed to the osteoblastic lineage, but also imply that TGF-beta 1 may be inhibitory to induction of osteogenic cells in vivo.     

Multiple recurrences of cervical intraepithelial neoplasia in women with the human immunodeficiency virus

OBJECTIVE: To evaluate the long-term outcomes after treatment of cervical intraepithelial neoplasia (CIN) in women infected with the human immunodeficiency virus (HIV). METHODS: Human immunodeficiency virus-infected and HIV-negative women treated for CIN by ablation or excision were followed-up prospectively by cytology and colposcopy for periods of up to 73 months. RESULTS: Among 127 HIV-infected CIN patients, 62% developed recurrent CIN by 36 months after treatment, compared with 18% of the 193 HIV-negative CIN patients. Recurrence rates reached 87% in 41 HIV-infected women with CD4 counts less than 200 cells/mm3. Progression to higher-grade neoplasia, including one invasive cancer, occurred by 36 months in 25% of HIV-infected and 2% of HIV-negative women. After adjusting for age, CIN severity, and treatment type, predictors of recurrence included HIV infection (rate ratio 4.4), and, in HIV-positive women, low CD4 count (rate ratio 2.2). In patients treated by excision, predictors of recurrence included HIV infection (rate ratio 2.0) and residual CIN after treatment (rate ratio 2.7). After a second treatment,a second CIN recurrence developed in 14 of 33 HIV-infected and in one of 17 HIV-negative women. After a third treatment, three of six HIV-infected women developed a third recurrence. With long-term follow-up, 45% of treated HIV-infected CIN patients had chronic condylomatous changes in the cervix compared with 5% of HIV-negative women. CONCLUSION: In HIV-infected women, CIN may recur despite multiple treatments, and chronic condylomatous changes are common. Innovative therapies for controlling CIN in HIV-infected women are needed.     

Epidermal growth factor receptor expression in cervical intraepithelial neoplasia and its modulation during an alpha-difluoromethylornithine chemoprevention trial

Chemoprevention trials designed to prevent progression to invasive cervical cancer will benefit from the identification of biomarkers that assess the risk of developing tumors, predict likelihood of response to treatment, and measure biological response to intervention. The purpose of this study was to examine expression of epidermal growth factor receptor (EGFR) as a marker for progression of cervical intraepithelial neoplasia (CIN) and as a surrogate end point biomarker in a chemoprevention trial with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase. To evaluate quantitative and spatial changes in EGFR expression during cervical tumorigenesis, paraffin sections from 42 archival cervical cone biopsies, each containing multiple stages of CIN, were immunohistochemically stained for EGFR, and the level and spatial expression of EGFR were quantitated by image analysis. In the progression from normal epithelium to CIN 1 to CIN 2 to CIN 3 to invasive cancer, EGFR expression showed two types of changes. Normal control epithelium showed EGFR expression predominantly confined to the basal layer, while histologically normal epithelium in specimens containing CIN showed relatively increased EGFR expression in the basal layer and the extension of EGFR expression away from the basal layer. The total EGFR relative staining intensity (RSI) of epithelium increased with the degree of CIN, predominantly due to a progressive expansion of EGFR-expressing cells away from the basal layer rather than an increase in the level of EGFR expression per cell. To determine whether EGFR expression would be modulated by a 1-month chemopreventive intervention with DFMO, pretreatment and posttreatment cervical biopsy specimens from 25 patients (22 evaluable) were examined for EGFR expression. Although the overall levels of EGFR expression were not modulated in either histological responders or nonresponders, responders showed a prominent down-regulation of EGFR expression away from the basal layer after DFMO treatment. Interestingly, pretreatment EGFR expression levels predicted for DFMO response [i.e., eight responses (72.7%) for 11 cases with RSI levels below 0.35 versus one response (9.1%) for 11 cases with RSI levels above 0.35 (P < 0.01)]. These results suggest that CIN progression is associated with a spatial dysregulation of EGFR expression that can be reversed by DFMO treatment, especially in patients whose pretreatment CIN 3 lesions exhibit relatively low EGFR expression.     

Immunohistochemistry with antibody to the LA-1 oncogene as a prognostic marker in cervical intraepithelial neoplasia

Previous studies with antibody to a synthetic peptide designated LA-1 identified a 60-kDa protein in cervical intraepithelial neoplasia and invasive cancer tissues. To determine whether these findings are of clinical significance cervical tissues from 223 patients with squamous intraepithelial lesion (SIL) or invasive carcinoma and 39 normal healthy cervical tissues were stained with antibody to LA-1 using the immunoperoxidase assay. Tissues from 52 patients with squamous carcinomas at other sites were used as controls. Staining was respectively observed in 46.4, 56.5, and 64.7% of patients with low-grade SIL, high-grade SIL, and invasive cancer. It was localized in the atypical epithelium involving a progressively larger extent of epithelium as a function of increased pathologic grade. Only 10.3% of the normal cervical tissues stained with anti-LA-1 antibody. Twenty-five patients that were lost to follow-up for 2-5 years after the original diagnosis were studied at the time of diagnosis (1 degree biopsy) and when they returned to the clinic (2 degrees biopsy). In the follow-up series, LA-1 staining was observed in both biopsies from 9/12 patients that progressed to a higher degree of atypia, while 9/11 patients whose lesions remained stationary were LA-1 negative. Our studies suggest that LA-1 might be a useful biological marker of cervical neoplasia.