Differential Expression Patterns of GATA3 in Uterine Mesonephric and Nonmesonephric Lesions.

GATA binding protein 3 (GATA3) is a recently described immunohistochemical marker that has proven useful in the characterization of breast and urothelial carcinomas. However, the expression pattern of GATA3 in mesonephric proliferations is largely unknown. The aim of this study was to examine the immunohistochemical expression of GATA3 in cervicovaginal mesonephric lesions and compare it to its expression in endocervical and endometrial adenocarcinomas and cervicovaginal endometriosis. A cohort of 107 cases, including 33 cases of mesonephric lesions and 74 cases of nonmesonephric lesions, was selected for the study. Of 33 mesonephric lesions, 31 (94%) cases (16 remnants, 12 hyperplasias, and 3 adenocarcinomas) were strongly and diffusely positive in tumor cell nuclei for GATA3. The remaining 2 mesonephric carcinosarcomas showed focal nuclear staining and rare nuclear positivity, respectively. Of 36 endocervical adenocarcinomas, 33 (92%) were negative for GATA3 and the remaining revealed focal weak nuclear staining. Of 34 endometrial adenocarcinomas, 32 (94%) were negative, whereas 2 showed rare nuclear positivity. All 4 cases of endometriosis were negative. The benign endocervical epithelium and the benign endometrium in most cases lacked GATA3 expression, whereas the benign squamous epithelium in the majority exhibited nuclear basal and parabasal staining pattern. Our study demonstrates that GATA3 protein is expressed in most mesonephric lesions, regardless of them being benign or malignant. In contrast, GATA3 is absent in the majority of endometrial and endocervical adenocarcinomas. These results support that GATA3 immunostain can be a useful tool in differentiating mesonephric lesions from endocervical and endometrial adenocarcinomas.

Host chemokine and cytokine response in the endocervix within the first developmental cycle of Chlamydia muridarum.

The initial host response in a primary chlamydial infection is the onset of acute inflammation. However, we still know very little about the early temporal events in the induction of the acute inflammatory response and how these events relate to the initial chlamydial developmental cycle in an actual genital infection. Because it was critical to initiate a synchronous infection in the endocervix in the first 24 h to evaluate the sequential expression of the host response, we developed the surgical methodology of depositing Chlamydia muridarum directly on the endocervix. Cervical tissue was collected at 3, 12, and 24 h after inoculation and the expression array of chemokines, cytokines, and receptors was assessed to characterize the response during the initial developmental cycle. Polymorphonuclear leukocyte (PMN) infiltration was first observed at 12 h after inoculation, and a few PMNs could be seen in the epithelium at 24 h. Electron microscopic analysis at 24 h showed that virtually all inclusions were at the same stage of development, indicating a synchronous infection. Several chemokine and cytokine genes were expressed as early as 3 h after infection, but by 12 h, 41 genes were expressed. Thus, activation of the host response occurs both with the introduction of elementary bodies into the host and early replication of reticulate bodies. No significant response was observed when UV-inactivated organisms were inoculated into the cervix at any time interval. This model provides an ideal opportunity to investigate the mechanisms by which the early inflammatory response is induced in vivo.

[The study of expression of apoptosis receptors (CD95+) on the surface of neutrophils from cervical secretion of women with chlamydial infection and the possibility of its correction by magnetic laser radiation].

The present work was designed to study the expression of CD95 antigen (Fas/APO-1) at the surface of neutrophil granulocytes from the cervical secretion. Sixty five female patients with Chlamydia infection available for observation exhibited enhanced CD95+ expression following basic therapy. It was found that combined treatment with the use of magnetic laser radiation normalized the level of CD95+ surface receptors on neutrophils.

Association between high risk papillomavirus DNA and nitric oxide release in the human uterine cervix.

OBJECTIVE: Local cervical factors may determine the outcome of human papillomavirus (HPV) infection. Nitric oxide (NO) may be one such factor, since it is produced by uterine cervical cells and it takes part in both immunological and carcinogenic reactions. We studied the association between the presence of cervical high risk (hr) HPV DNA and NO in the cervical canal in women. METHODS: High risk HPV DNA status was assessed from 328 women by using a specific DNA test and the release of cervical NO was assessed as nitrate/nitrite in cervical fluid. Cervical NO was then compared between women showing different status of hr HPV DNA and different cytological and histological findings. RESULTS: High risk HPV DNA was present in 175/328 (53%) women. The cervical NO release in women with hr HPV DNA was 90% higher compared to hr HPV DNA negative women (p<0.001) (median 45.2 micromol/L; 95% CI 35.2-53.1 vs. 23.8 micromol/L; 95% CI 21.0-26.1). This elevation was not affected by parity, use of oral contraception, intrauterine devices, or signs of bacterial vaginosis or candida infection. Cytologically healthy epithelium and epithelium with mild cytological or histological changes showed elevated NO release if hr HPV DNA was present. CONCLUSIONS: The presence of hr HPV DNA is associated with an increased release of NO in the human uterine cervix. The clinical significance of this phenomenon remains open.

P16 immunostaining patterns in microglandular hyperplasia of the cervix and their significance.

P16 immunostaining is an important adjunct in the differential diagnosis of difficult squamous and glandular intraepithelial lesions of the cervix. However, unexpected staining of epithelium other than the target lesion can pose a problem in the interpretation. This study examined a common entity in the cervix, microglandular hyperplasia (MGH), that is associated with proliferations of both columnar and squamous epithelial cells-and ascertained the frequency of p16 staining, its pattern, and relationship to human papillomavirus. Fifty-seven cases of MGH were analyzed; 25 scored strongly immunopositive (44%). In 18, staining of the superficial columnar epithelium was patchy, involving 10% to 20% of cells on the surface; in 4 cases, 30% to 40% of cells; and in another 3, over 50% of the cells in a given area were strongly positive. Staining involved both nucleus and cytoplasm of columnar cells. P16 positivity did not colocalize with either cyclin E or MIB-1. Adjacent non-MGH-related columnar epithelium scored negative for p16. Of 25 p16-positive columnar epithelia analyzed, all were human papillomavirus -negative. In conclusion, benign columnar epithelium in the setting of MGH can be expected to stain strongly for p16. Practitioners should be aware of this when evaluating diagnostically difficult squamous or glandular epithelial changes occurring in the setting of MGH or when interpreting cytologic preparations stained with p16.

Meta-analysis of the accuracy of p16 or p16/Ki-67 immunocytochemistry versus HPV testing for the detection of CIN2+/CIN3+ in triage of women with minor abnormal cytology.

BACKGROUND: Women with atypical squamous cells of undetermined significance (ASC-US) can be triaged accurately with a high-risk human papillomavirus (hrHPV) test to identify those who need a referral. However, the triage of low-grade squamous intraepithelial lesion (LSIL) with hrHPV testing has very low specificity. Overexpression of p16, with or without Ki-67, indicates neoplastic transformation of human papillomavirus-infected cervical cells and may more accurately predict underlying cervical intraepithelial neoplasia of grade 3 or worse (CIN3+). METHODS: A literature search was conducted in 3 bibliographic databases. Studies were selected if they included women with ASC-US or LSIL who were triaged with dual staining (p16/Ki-67) and/or p16 staining and, if available, with a comparator hrHPV test to detect cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) or CIN3+. RESULTS: Thirty-eight studies were eligible. The sensitivity of p16 staining for CIN3+ was significantly lower than that of hrHPV DNA testing (ratio for ASC-US, 0.87; 95% confidence interval [CI], 0.78-0.97; ratio for LSIL, 0.86; 95% CI, 0.80-0.93). In contrast, the specificity of p16 staining was substantially higher with relative specificities of 1.60 (95% CI, 1.35-1.88) and 2.29 (95% CI, 2.05-2.56) for ASC-US and LSIL respectively. Dual staining was as sensitive as hrHPV DNA testing but was more specific (ratio for ASC-US, 1.65; 95% CI, 1.42-1.92; ratio for LSIL, 2.45; 95% CI, 2.17-2.77). CONCLUSIONS: This meta-analysis confirms that p16 staining and p16/Ki-67 staining are more specific for CIN2+/CIN3+ than hrHPV DNA testing. Although p16 staining is less sensitive for CIN3+ than hrHPV DNA testing, dual staining has similar sensitivity.

Effect of chronic pretreatment with 17ß-estradiol and/or progesterone on the nociceptive response to uterine cervical distension in a rat model.

It is widely known that visceral pain is more prevalent in women than in men, and this phenomenon is interpreted as a consequence of the gonadal hormone modulation of pain perception and transduction. Uterine cervical distension might cause obstetric and gynecologic pain with clinical relevance to visceral pain. In this study, we focused on the roles of 17ß-estradiol and progesterone in visceral nociception with the use of a rat model of uterine cervical distension. Female ovariectomized rats were injected with 17ß-estradiol (E2) or progesterone (P4) for 21 days, after which visceral pain-induced spinal c-fos expression and visceromotor reflex changes were compared between ovariectomized and hormone-substituted groups. We found that uterine cervical distension induced a drastic increase in spinal c-fos expression and visceromotor reflex activity, and ovariectomy inhibited the increase in c-fos expression induced by visceral pain; this inhibition was reversed by estrogen but not progesterone replacement. This study demonstrates that estrogen is involved in uterine cervical nociception, while progesterone plays less of a significant role.

[Comparative proteome analysis of human papillomavirus-infected cervical specimens and the difference between the high- and low-risk genotypes of human papillomavirus].

OBJECTIVE: To perform an comparative proteome analysis of human papillomavirus-infected cervical specimens and to investigate different expressions between high- and low-risk genotypes. METHODS: The cervical specimens were divided into two groups (cervical intraepithelial neoplasia group and condyloma acuminatum group) according to their genotypes. Using comparative proteome technology, high-risk human papillomavirus-infected cervical intraepithelial neoplasia, low-risk human papillomavirus-infected condyloma acuminatum, and normal cervical intraepithelial tissue were compared. The differential expression protein spots were identified by mass spectrometry. RESULTS: Totally 26 differential spots were selected and analyzed, and 22 peptide mass fingerprints (PMF) maps were obtained by MALDI-TOF-MS. Eighteen proteins were preliminarily identified after searching the NCBInr database. The function information of these 18 proteins mainly involved cell metabolism, signal transduction, cell secretion, cell cytoskeleton construction, cell proliferation, and apoptosis. CONCLUSION: The proteomic expressions after the cervical infection of high- or low-risk genotype of human papillomavirus are obviously different.

Intra-uterine fluid collection in postmenopuasal women with cervical stenosis.

OBJECTIVES: The aim of the study was to assess the clinical significance of intra-uterine fluid collection in postmenopausal women with cervical stenosis with and without vaginal bleeding. METHODS: A group of 82 consecutive postmenopausal women with cervical stenosis and sonographically confirmed intra-uterine fluid collection underwent D&C with or without hysteroscopy. Diagnostic hysteroscopy was performed in all patients with an endometrial thickness (ET) was greater than 8mm, or with irregular endometrium at any degree of ET. The patients were divided and evaluated prospectively into two groups according to the presence or absence of postmenopausal bleeding (PMB). Twenty-six women were with PMB and 56 women were asymptomatic. RESULTS: The groups were similar as far as endometrial thickness and histopathological results were concerned. Atrophic endometrium was found in 69 patients (84%), 23 in the PMB group (89%) and 46 in the other group (82%), proliferative endometrium in 7 (9%) and endometrial polyps were found in 35 patients (43%), 12 in the PMB group (46%) and 23 in the other group (41%). When ET was > or =8 mm, in 93% of the cases an endometrial polyp was found (25 out of 27). No case of endometrial cancer was found. A premalignant condition was diagnosed in one patient with an endometrial polyp in the PMB group. All patients with endometrial thickness of less than 3 mm in ultrasound had atrophic endometrium. The incidence of intrauterine pathology increased with the increasing thickness of endometrium as observed by ultrasound. CONCLUSIONS: The presence of intra-uterine fluid collection in postmenopausal patients with cervical stenosis seems to be a benign condition. Normal endometrium of less than 3mm observed by ultrasound in postmenopausal women without vaginal bleeding does not necessarily need further surgical investigation.

Overriding of cyclin-dependent kinase inhibitors by high and low risk human papillomavirus types: evidence for an in vivo role in cervical lesions.

High risk types of human papillomavirus (HPV) are agents in the aetiology of cervical carcinoma. The products of two early genes, E6 and E7, appear to be the principal transforming proteins. Studies of various monolayer cell culture systems have shown that the E7 oncoprotein of human papillomavirus type 16 is able to neutralize or bypass the inhibitory effect of the cell cycle-dependent kinase (CDK) inhibitors (CKIs) p21WAF1/CIP1 and p27KIP1. To understand whether the p21WAF1/CIP1 or p27KIP1 neutralization also plays a role in vivo, we performed studies on clinical specimens. Forty-five cervical biopsies, including HPV-negative mucosa, HPV 16-positive preinvasive (low and high grade lesions) and invasive neoplasia as well as HPV 6-positive condyloma acuminatum were analysed by single and double immunohistology. We examined the positive cell cycle regulator cyclin A and the universal cell cycle marker Ki67 as well as the negative cell cycle regulators p21WAF1/CIP1 and p27KIP1. Here, we show that in a significant fraction of cells the G1 block can be overcome despite high levels of CKIs in HPV lesions. This phenomenon, which was more evident for p21WAF1/CIP1 than for p27KIP1 was most marked in low grade lesions and in condylomata acuminata, in which a high viral productivity is expected. These results indicate that the overriding of CKI inactivation by viral oncoproteins appears to be a conserved property between low and high risk HPV types. We conclude that the CKI neutralization by HPVs is likely to be required for viral DNA replication rather than for malignant transformation of the host cell.

Concentrations of carotenoids, tocopherols, and retinol in paired plasma and cervical tissue of patients with cervical cancer, precancer, and noncancerous diseases.

Paired blood (collected after an overnight fast) and cervical tissue (cancerous, precancerous, and noncancerous) samples were obtained from 87 patients (age, 21-86 years) who had a hysterectomy or biopsy due to cervical cancer, precancer (cervical intraepithelial neoplasia I, II, and III), or noncancerous diseases. The samples were analyzed using high-performance liquid chromatography for 10 micronutrients (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, cis-beta-carotene, alpha-tocopherol, gamma-tocopherol, and retinol). The results indicated that: (a) among the three patient groups, the mean plasma concentrations of all micronutrients except gamma-tocopherol were lowest in the cancer patients; however, the mean tissue concentrations of the two tocopherols and certain carotenoids were highest in the cancerous tissue; and (b) among the 10 micronutrients, only the concentrations of beta-carotene and cis-beta-carotene were lower in both the plasma and tissue of cancer and precancer patients than in those of noncancer controls. These results suggest that: (a) not all of the micronutrient concentrations in plasma reflect the micronutrient concentrations in cervical tissue; thus, in some cases, it may be necessary to measure the tissue micronutrient concentrations to define the role of the micronutrients in cervical carcinogenesis; and (b) maintaining an adequate plasma and tissue concentration of beta-carotene may be necessary for the prevention of cervical cancer and precancer.

MUC4 expression is increased in dysplastic cervical disorders.

The female uterine cervix has 2 characteristic populations of epithelial cells: the endocervix is composed by mucus-secreting cells that express several mucin genes, and the exocervix has a typical stratified squamous epithelium and does not express secreted mucins. Among human mucin genes, the MUC4 sequence has a transmembrane domain, and its molecular structure suggests that it has a protective role and also may be implicated in intracellular signalling. The aim of this study is to analyze whether changes in the expression of MUC4 can be detected associated with the squamous dysplastic transformation of exocervical epithelium. MUC4 expression has been analyzed by immunohistochemistry, Western blotting, and in situ hybridization. Using immunohistochemical techniques, MUC4 is found in normal endocervix (n = 11) and is absent or only focally detected in the normal stratified cervical epithelium (n = 18). In samples from squamous metaplasia (n = 9), MUC4 is variably expressed (10% to 50% positive cells), whereas MUC4 is strongly detected in dysplastic cervical epithelia. The greatest number of positive cells is found in samples with moderate and severe dysplasia in which MUC4 is detected in 100% of the analyzed samples (n = 16). These results have been confirmed by Western blotting and by detection of MUC4 transcripts using in situ hybridization. The present data suggest that MUC4 is activated during the process of squamous dysplastic transformation and may be used as a marker for this pathologic process.

Papillary immature metaplasia (immature condyloma) of the cervix: a clinicopathologic analysis and comparison with papillary squamous carcinoma.

Papillary immature metaplasia (PIM) is a variant of human papillomavirus (HPV) 6 or 11 infection. PIM resembles an immature metaplasia but has filiform papillae, variable cytological atypia, and, frequently, extension into the endocervical canal. Because the unusual morphology and presentation of PIM may cause confusion between this and other benign and malignant papillary neoplasms, we conducted a clinicopathologic analysis of PIM and compared expression of Ki-67 between PIM, condyloma, and papillary carcinoma. Data on patient age, duration of the lesions, and procedures, including cone biopsy, were obtained. The distribution and intensity of staining for Ki-67 in the epithelium was recorded and compared with both condyloma and papillary carcinoma. HPV typing was performed by polymerase chain reaction (PCR) and restriction fragment length pleomorphism analysis (RFLP). Ten of 13 PIMs were HPV 6/11 positive. Three cases contained areas closely resembling condyloma. Eleven cone biopsies were performed on nine cases. Three were found to have a coexisting high-grade squamous intraepithelial lesion that was either HPV 6/11 negative or contained another HPV type. All PIMs displayed variable staining for Ki-67 with a low index of staining in the mid and upper epithelial layers. In contrast, areas of condyloma had significantly stronger staining in areas with viral cytopathic effect (koilocytosis). Six papillary carcinomas were analyzed and displayed moderate to diffuse staining, including staining of the superficial cell nuclei. PIM is a distinct pathological subset of cervical condyloma that frequently is managed by cone biopsy and may persist. The marked reduction in Ki-67 staining in superficial cell layers distinguishes PIM from some condylomata and most HSILs and papillary carcinomas. Immunostaining thus may be helpful in distinguishing PIM from papillary carcinoma, although the differentiation of the two is best made on morphological grounds.

Extensively keratinized squamous intraepithelial lesions of the cervix are difficult to grade.

We tested the hypothesis that extensively keratinized squamous intraepithelial lesions (SILs) are difficult to grade precisely by identifying 100 Papanicolaou smears with a keratinizing SIL that had been originally judged difficult to grade. Of these, 65 were confirmed as low-grade SIL (LSIL) or high-grade SIL (HSIL) on subsequent biopsy. The 65 smears were reviewed independently by 3 cytopathologists who graded each case as LSIL or HSIL (by Bethesda System criteria). The accuracy of the grade was determined by the subsequent biopsy results; accuracy was compared with that of a historic control group of SILs with biopsy follow-up. In the study group, biopsies showed LSIL in 41 cases and HSIL in 24. The mean accuracy for a smear diagnosis of LSIL was 60% for the study group and 92% for the control group. For a smear diagnosis of HSIL, the accuracy was 60% for the study group and 95% for the control group. The overall kappa value for the study group confirmed poor interobserver agreement. Some keratinizing SILs are difficult if not impossible to grade precisely using standard criteria. For such lesions, the diagnosis "SIL, grade cannot be determined due to extensive keratinization" is justified.

Patterns of keratin 19 expression in normal, metaplastic, condylomatous, atrophic, dysplastic, and malignant cervical squamous epithelium.

Keratin 19 (K-19) expression has been strongly correlated with dysplasia in oral epithelium. Expression of K-19 was evaluated by immunoperoxidase staining in formalin-fixed normal ectocervical tissue, normal endocervical tissue, cervical dysplasia, squamous metaplasia, atrophic epithelium, cervical condylomas, and invasive carcinoma to determine if a correlation of K-19 expression with dysplasia was present in the cervical epithelium. Uniform expression of K-19 was seen in endocervical epithelium and in the basal layer of normal ectocervical epithelium in all areas where these epithelia were present. Cervical dysplasia without associated condylomatous changes showed increased expression of K-19 in suprabasal epithelium, corresponding to the level of immature cells. Squamous metaplasia was characterized by scattered cells with increased staining (patch-quilt pattern). There was considerable overlap in the patterns of K-19 expression in dysplastic and metaplastic epithelium. Thus K-19 staining pattern could not be used as a distinctive marker for dysplasia in the cervical epithelium. Atrophic epithelium showed a characteristic uniform but low-level expression of K-19 in suprabasal areas. This pattern may be of diagnostic use in differentiating atrophic lesions from dysplasia. Condylomas showed focal loss of K-19 in the basal layer, suggesting induction of premature differentiation in the basal layer by human papillomavirus infection. Invasive carcinomas showed variable patterns. K-19 is a marker of immature cervical squamous epithelium, with generally distinctive but sometimes overlapping patterns of expression in various diagnostic categories.

Cytokeratin expression and acetowhite change in cervical epithelium.

AIM: To investigate the distribution of cytokeratins 10, 13, 14 and 19 in biopsy specimens taken from acetowhite and non-acetowhite areas of the cervix. METHOD: Cervical biopsy specimens were taken from both acetowhite and non-acetowhite areas from 44 patients who presented with abnormal cervical cytology. The specimens were snap frozen in liquid nitrogen and multiple sections taken from each specimen. Staining was performed for cytokeratins 10, 13, 14, 19 and NADPH diaphorase enzyme. The areas of each section positive for the various markers were measured. RESULTS: Cytokeratin 10 positive cells were greatly increased in number in acetowhite biopsy specimens compared with non-acetowhite samples (45.1% v 2.8%; p < 0.0001). Cytokeratin 19 was also increased, but to a lesser extent (17.8% v 5.5%; p < 0.0001). In contrast, the almost universal expression of cytokeratin 13 was reduced in acetowhite biopsy specimens (86.2% v 96.9%; p < 0.0001). Cytokeratin 14 was found diffusely in the basal region of the stratified squamous epithelium and was marginally more apparent in the acetowhite biopsy specimens (p = 0.04). CONCLUSION: It is suggested that the presence of cytokeratin 10 may be an essential requirement for the formation of acetowhite change in association with the cellular swelling caused by acetic acid.

The many faces of atrophy in gynecologic cytology.

As more attention is paid to cervical cancer screening in the postmenopausal population, increased numbers of atrophic specimens will be evaluated in the cytology laboratory. In addition, specimens that have cell patterns that mimic the nonestrogen or partially estrogen-stimulated state occur in a variety of situations, including pregnancy, the postpartum period, and in individuals who are treated with progesterone. A firm understanding of the cellular changes that are within the range of normal in such circumstances is critical to ensure the specificity of interpretation. This article has detailed the conditions under which nonestrogen stimulated patterns occur and addressed the cytologic changes that are noted. Hints to avoid pitfalls have been offered. There is no substitute for a thorough evaluation of each case, and with continued experience and understanding of these principles, the correct interpretations, and, ultimately, correct management of patients, can be optimized.

Unusual endocervical lesions with endocrine cells.

Four cases of unusual lesions of endocervix are presented. They were all incidental findings, showing no obvious infiltrative and metastatic properties to attest their malignant nature. Two lesions were entirely confined to the endocervical mucosa. The main characteristics of these proliferative processes thus were an abnormal architecture with branched or small glands, a hypermucinous benign-appearing epithelium of endocervical type, and stromal smooth-muscle. In contrast with normal endocervical mucosa, all lesions contained prominent and variegated endocrine cells. These 4 cases were quite comparable to 3 other observations previously reported. This homogeneous group of endocervical lesions does not correspond to a well-defined type of endocervical neoplasia. It shares morphological analogies with adenoma malignum. The relationship with adenoma malignum as well as with some other gynaecological neoplasms is discussed. The recognition of these small-sized and highly differentiated lesions is largely facilitated by the use of the Grimelius reaction to detect argyrophilic cells.

Immunolocalization of cystatin A in neoplastic, virus and inflammatory lesions of the uterine cervix.

Cystatin A was immunohistochemically demonstrated in the normal squamous epithelium of the uterine cervix, particularly in the parabasal and superficial cell layers whereas it was absent or scanty in the basal cells and in areas with parakeratosis. Cystatin A was also found in neoplastic lesions (dysplasia, carcinoma in situ and squamous cell carcinoma), but less abundant than in normal squamous epithelium. The immunoreaction in intraepithelial neoplasia was closely related to the degree of morphological maturation of the squamous cells with more abundant cystatin A in low grade dysplasia and less in high grade dysplasia and carcinoma in situ. In squamous cell carcinoma, cystatin A was often abundant in highly differentiated areas and almost absent in poorly differentiated ones. Cystatin A was found in the squamous epithelium in herpes and in condylomatous lesions. It was also found in the cytoplasm of neutrophils, but not in lymphocytes and plasma cells. In unspecific cervicitis, cystatin A was found extracytoplasmatically as small vesicles in the epithelial-stromal junction. The implications of cystatin A in neoplastic, virus, and inflammatory processes are discussed.

Patterns of mucous secretion in normal and pathological conditions of the endocervix.

20 specimens of normal endocervix, 30 of chronic cervicitis, 20 of endocervical polyps and 10 of adenocarcinomas were histochemically investigated in order to assess their mucin pattern. Diastase periodic acid-Schiff (D-PAS), Alcian blue pH 2.5 (AB), High iron-diamine (HID) and HID followed by Alcian blue pH 2.5 (HID-AB) were used. Both the superficial and glandular epithelium of the normal endocervix contained abundant amounts of neutral mucins. Generally sialomucins were scarce and predominant over sulphomucins: the latter were in some cases absent in the proliferative phase of the menstrual cycle and increased in the secretory phase. In chronic cervicitis a slight amount of sulphomucins in the residual glandular epithelium, especially in areas presenting severe inflammation, pseudoerosion, or both was observed. Nabothian cysts mainly contained sulphomucins. In the endocervical polyps, the mucin pattern was various. In adenocarcinomas mucin secretion was usually scanty and mixed with a predominance of sialomucins. Therefore resulted: the mucin pattern of the normal endocervical epithelium is related to the menstrual cycle; the histochemical evaluation of mucous secretion, presently doesn't seem to be helpful in differentiating endocervical from endometrial adenocarcinomas.