Plasmacytoid Urothelial Carcinoma of the Urinary Bladder Metastatic to the Duodenum: A Case Report-Diagnostic Relevance of GATA3 Immunohistochemistry.

Plasmacytoid urothelial carcinoma (PUC) of the urinary bladder is a rare and aggressive subtype of urothelial carcinoma. Its deceptive morphology is characterized by a discohesive growth of cells with plasmacytoid morphology. Since this tumor might be confused with plasmacytoma, lymphoma, or carcinoma variants, appropriate diagnosis in small biopsy samples could be challenging. This study reports the case of a 53-year-old man who presented with frequent nocturnal urgency, without hematuria. A transurethral bladder and a prostate resection specimen displayed infiltration of neoplastic cells in a spray-like discohesive pattern with occasional formation of small irregular nests and cord-like arrangements. The basic morphology of the tumor cells was plasmacytoid, with eccentric nuclei and eosinophilic cytoplasm. Tumor cells grew through the lamina muscularis mucosae, with splintering of the bladder wall musculature and infiltration of prostatic tissue. They displayed strong and diffuse nuclear reactivity for p53 and GATA3. Eight months after surgery, the patient experienced upper abdominal discomfort. A duodenal biopsy showed infiltration of plasmacytoid atypical cells strongly immunoreactive for GATA3, consistent with the previously diagnosed PUC. The patient died eleven months after the primary diagnosis of his PUC of tumor cachexia losing about 50% of his original body weight, furthermore, with ascites and intraperitoneal tumor spread.

Tumor necrosis factor-α expression in patients with obstructive benign prostatic hyperplasia is associated with a higher incidence of asymptomatic inflammatory prostatitis NIH category IV and prostatic calcification.

OBJECTIVE: The aim of this study was to investigate the association of the expression of tumor necrosis factor-α (TNF-α) with asymptomatic inflammatory prostatitis National Institutes of Health (NIH) category IV and prostatic calculi, in patients with obstructive benign prostatic hyperplasia (BPH) treated by transurethral electroresection of the prostate (TURP). MATERIALS AND METHODS: Ninety-six patients with obstructive BPH and TURP were evaluated in a prospective study. Based on a preoperative transrectal ultrasound examination of the prostate gland, patients were divided into two groups, one with prostatic calculi (n = 31) and one without (n = 65). Prostatitis NIH category IV was classified according to Irani's histological grading system (Irani et al. J Urol 1997;157:1301-3). Associations between the incidence of prostatic calculi, histological prostatitis, TNF-α expression, prostate-specific antigen, uric acid, cholesterol, triglycerides, C-reactive protein, International Prostate Symptom Score (IPSS), the International Index for Erectile Function (IIEF-5) and the NIH-Chronic Prostatitis Symptom Index Score (NIH-CPSI) were analyzed. RESULTS: Prostatitis was confirmed by histological investigation in 71.9% of patients: 83.9% of those with prostatic calculi versus 66.1% of those without (p < 0.04). TNF-α expression was significantly higher in patients with prostatic calculi. Association calculations yielded significant values for the severity (histological grading) of inflammation (p < 0.029), TNF-α expression (p < 0.007), uric acid (p < 0.005), cholesterol (p < 0.028) and the NIH-CPS subdomain of urinary symptoms (p < 0.044) in patients with prostatic calculi. CONCLUSIONS: In patients with obstructive BPH, prostatic calculi were found on ultrasound in one-third of the cases, and histological NIH category IV prostatitis in two-thirds of cases. The incidence of both prostatitis NIH category IV and TNF-α expression was significantly higher in patients with prostatic calculi than in those without.

p40 as a Basal Cell Marker in the Diagnosis of Prostate Glandular Proliferations: A Comparative Immunohistochemical Study with 34betaE12.

Immunohistochemistry is important for the accurate diagnosis of basal cells in atypical glandular proliferations of the prostate. p40, an isoform of p63, may be an adjunct to a marker panel in this setting. Biopsies of 68 patients were analyzed by immunohistochemistry using antibodies to 34betaE12 and p40. Basal cell staining was classified as negative, partial (<60%), or diffuse (≥60%); irregular staining was defined as discordant staining patterns. In acinar proliferations (N = 41), partial staining for both markers was seen in 42%, and diffuse staining in 46% of reactive cases. An irregular reactivity was noted in one case only (2%). Finally, these lesions were signed out as benign. Acinar proliferations negative for both markers and limited amount of glands (≤4) were termed atypical small acinar proliferations (ASAP). Out of six PIN lesions two cases showed partial, three cases showed diffuse reactivity for both markers, and one case was stained irregular. All cases diagnosed as prostate carcinomas (N = 20) had no evidence of basal cell staining for neither of the markers. p40 expression is closely correlated to 34betaE12 with respect to demonstration of basal cells of prostate glands and may provide further information on the dignity of glandular proliferations of the prostate.

Epithelial and tumor-associated endothelial expression of B7-H3 in cervical carcinoma: relation with CD8+ intraepithelial lymphocytes, FIGO stage, and phosphohistone H3 (PHH3) reactivity.

B7-H3 is a transmembrane protein and a member of the B7 family of immune regulatory ligands. It exerts both inhibitory and stimulatory effects on the activation of T cells. We investigated the expression of B7-H3 in invasive squamous cell carcinoma (ISCC) of the uterine cervix by immunohistochemistry, and aimed to determine whether expression of this factor is involved in the progression of the morphologic spectrum from normal cervical epithelia to cervical intraepithelial neoplasia and cervical ISCC. In addition, we sought to examine the relation of B7-H3 to the abundance of tumor-infiltrating and tumor-associated CD8(+) lymphocytes and to the evidence of phosphohistone H3, which is a core histone protein detected during mitosis. B7-H3 immunostaining was scored with regard to quantity and intensity of positively stained cells, and was noted in membranous and cytoplasmic patterns in epithelial cells and on endothelia of stromal blood vessels. Compared with those in intraepithelial neoplasias, immunoscores were significantly increased in ISCC (P<0.0001 for epithelial and endothelial expression, respectively). High scoring was associated with International Federation of Gynecology and Obstetrics stages IB and higher. Immunoscores of epithelial and endothelial B7-H3 expression were correlated significantly (P=0.0358). Epithelial and endothelial expression of B7-H3 was inversely related with CD8(+) tumor-infiltrating lymphocyte (P<0.0001). Moderate/strong B7-H3 epithelial as well as endothelial expression was mutually increased with intermediate/strong phosphohistone H3 scores (P=0.0396 and P=0.0483, respectively). There was no statistical relation with survival; however, no patient with negative scoring died of her tumor. Our results indicate that B7-H3 expression in cervical ISCC may play an important role in overcoming CD8(+) T-cell immunoregulation to acquire aggressive growth.

Immunohistochemical expression of interleukin-2 receptor and interleukin-6 in patients with prostate cancer and benign prostatic hyperplasia: association with asymptomatic inflammatory prostatitis NIH category IV.

OBJECTIVE: This study prospectively investigated the immunohistochemical expression of interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6) in patients with prostate cancer and benign prostatic hyperplasia (BPH), and a possible association of these conditions with asymptomatic inflammatory prostatitis National Institutes of Health (NIH) category IV. MATERIALS AND METHODS: The study included 139 consecutive patients who underwent transurethral resection of the prostate and transvesical enucleation of the prostate (n = 82) or radical prostatectomy (n = 57). To characterize inflammatory changes the criteria proposed by Irani et al. [J Urol 1997;157:1301-3] were used. IL-2R and IL-6 expression was studied by a standard immunohistochemical method. Results were correlated with tumour, node, metastasis stage, Gleason scores, total prostate-specific antigen, International Prostate Symptom Score and body mass index. RESULTS: IL-2R and IL-6 expression was significantly higher in neoplastic prostate cancer tissue than in normal tissue of prostate cancer patients (p < 0.001 and p < 0.04, respectively). Prostate cancer patients with prostatitis showed significantly higher IL-2R expression than those without inflammation (p < 0.03). In patients with BPH, expression of IL-2R as well as IL-6 was higher in patients with prostatitis than in those without (p < 0.01 and p < 0.02, respectively). CONCLUSIONS: IL-2R and IL-6 expression was significantly higher in prostate cancer tissue than in normal tissue. Patients with asymptomatic inflammatory prostatitis NIH category IV showed significantly greater activity.

Ovarian carcinosarcoma associated with bilateral tubal intraepithelial carcinoma: a case report.

Carcinosarcomas (malignant mixed müllerian tumors) of the ovary are rare tumors. This report describes a case of a 64 years old patient presenting with a large tumor in the true pelvis, intraoperatively originating from the right ovary, with peritoneal metastatic deposits. Histologically, a dominant sarcomatoid component consisted of short spindle and epithelioid round cells. The nuclei were round to oval, with pleomorphism, hyperchromasia and frequently conspicuous nucleoli. Mitotic activity was brisk. The cells were aligned in hypercellular to myxoid hypocellular arrangements. Large epithelioid cells displayed abundant deeply eosinophilic cytoplasm and mono- to multinucleation. Immunohistochemically, these cells displayed strong reactivities for desmin, WT1 in a cytoplasmic staining pattern, p16, and vimentin. A second and minor tumor component revealed epithelial differentiation with mixed serous- endometrioid and squamous features, and immunohistochemical staining for AE1/AE3 cytokeratin, focally for p16 and p53(ink4), for nuclear WT1 in varying quantities, and weakly for vimentin. The fallopian tubes were remarkable for circumscribed areas of serous tubal intraepithelial carcinoma (STIC), found at the fimbria of the right and in the tubal mucosa close to the fimbria of the left tube. The final diagnosis was carcinosarcoma of the right ovary (malignant müllerian mixed tumor, heterologous type), with rhabdomyosarcomatous differentiations, FIGO stage IIIC. The patient died of recurrent tumor seven month after primary presentation.

Immunohistochemical expression of SOX2 in vulvar intraepithelial neoplasia and squamous cell carcinoma.

SOX2 is a transcription factor controlling pluripotency in both embryonic stem cells and adult tissue-specific stem cells. SOX2 has been reported as an important factor in squamous cell carcinomas (SCC) of different locations and is involved in tumorigenesis. We evaluated the expression of SOX2 in vulvar non-neoplastic and neoplastic epithelia to test whether it is related to neoplastic progression. SOX2 immunoexpression was evaluated in 101 formalin-fixed, paraffin-embedded archival vulvar epithelia consisting of normal squamous vulvar epithelia (n=25), lichen sclerosus (n=9), high-grade classic vulvar intraepithelial neoplasia (HG-VIN, n=16), differentiated vulvar intraepithelial neoplasia (d-VIN, n=18), and vulvar invasive keratinizing SCC (n=33). Immunoexpression of SOX2 was nuclear and increased stepwise from normal vulvar epithelia/lichen sclerosus to HG-VIN and d-VIN (P<0.0001), from HG-VIN and d-VIN to invasive SCC (P=0.0029), and followed the morphologic distribution of atypical squamous epithelial cells. Scores for normal vulvar epithelia versus lichen sclerosus and HG-VIN versus d-VIN, respectively, did not differ significantly. SOX2 expression increased from tumor Grade 1 to 3 (P=0.0124); there was no relation to recurrence and survival. This is the first study presenting SOX2 as overexpressed in vulvar intraepithelial and invasive squamous lesions. This overexpression apparently reflects an early event in the neoplastic transformation of vulvar squamous epithelia. However, SOX2 seems to play a role in histologic dedifferentiation to Grade 3 invasive SCC too, and may be relevant to vulvar carcinogenesis.

Expression of human telomerase reverse transcriptase in vulvar intraepithelial neoplasia and squamous cell carcinoma: an immunohistochemical study with survivin and p53.

CONTEXT: Human telomerase reverse transcriptase (hTERT), an enzyme that enables cells to overcome replicative senescence and to divide indefinitely, is overexpressed in many cancers and their precursor lesions. OBJECTIVE: To test whether hTERT expression is related to neoplastic progression and resistance to apoptosis in vulvar epithelia. DESIGN: Immunoexpression of hTERT was evaluated in 101 formalin-fixed, paraffin-embedded archival vulvar epithelia consisting of normal squamous vulvar epithelia (n  =  25), lichen sclerosus (n  =  10), high-grade classic vulvar intraepithelial neoplasia (n  =  16), differentiated vulvar intraepithelial neoplasia (n  =  18), and vulvar invasive keratinizing squamous cell carcinoma (n  =  32) and related to survivin and p53 expression. Immunostaining for all factors was scored for moderate and strong intensities with regard to quantity to determine upregulation and overexpression (score 0, 0% immunoreactive cells; score 1+, <5% immunoreactive cells; score 2+, 5% to 50% immunoreactive cells; score 3+, >50% immunoreactive cells). Score 3+ was considered as overexpression. RESULTS: Nuclear hTERT immunoexpression was closely related to survivin reactivity, increased from normal vulvar squamous epithelia to lichen sclerosus and to high-grade classic vulvar intraepithelial neoplasia, differentiated vulvar intraepithelial neoplasia, and invasive keratinizing squamous cell carcinoma (P < .001), and followed the morphologic distribution of atypical squamous epithelial cells. Overexpression of hTERT was comparable to that seen for p53 in invasive keratinizing squamous cell carcinoma (P  =  .62); significant differences were calculated for differentiated vulvar intraepithelial neoplasia (P  =  .003) and high-grade classic vulvar intraepithelial neoplasia (P  =  .001). CONCLUSION: Human telomerase reverse transcriptase is upregulated in vulvar intraepithelial neoplasia and invasive keratinizing squamous cell carcinoma compared with nonneoplastic squamous epithelia of the vulva as an apparently early and preinvasive event in the neoplastic transformation, with development of cellular longevity and resistance to apoptosis by survivin activation as associated features, independent of the etiology of vulvar intraepithelial neoplasia.

Immunoexpression of B7-H3 in endometrial cancer: relation to tumor T-cell infiltration and prognosis.

OBJECTIVE: B7-H3, a member of the B7 family of immune regulatory ligands regulates T cell-mediated peripheral immune response. The purpose of this study was to correlate the expression of B7-H3 and number of lymphocytes in patients with endometrial cancer. MATERIAL AND METHODS: A total of 107 patients with primary endometrial carcinoma (type I/endometrioid, n=81; type II, n=18) and endometrial hyperplasia (n=8) were investigated. Expression of B7-H3 in endometrial hyperplasia, endometrial carcinoma, and the endothelium of tumor-associated vasculature was assessed using immunohistochemistry from paraffin-embedded tissue blocks. Detection of CD8-positive tumor-infiltrating lymphocytes (TIL) and CD8-positive tumor-associated lymphocytes (TAL) was correlated with the expression of B7-H3. RESULTS: Patients with high grade tumors and patients with type II carcinomas expressed significantly more B7-H3 than low grade and endometrioid tumors (p=<0.0001 and p=0.0001, respectively). The expression of B7-H3 in the endothelium of identified vasculature in the tumor specimens showed similar results with strong relation to high grade tumors (p=0.001) and type II carcinomas (p=0.004). We found a significant correlation between B7-H3 expression on cancer cells and tumor T-cell infiltration (TIL) (p=0.017). In a univariate survival analysis, overexpression of B7-H3 in tumor cells was associated with shortened overall survival (p=0.005). CONCLUSIONS: B7-H3 is overexpressed on cancer cells and in the endothelium of tumor-associated vasculature in high grade tumors (G3) and type II carcinomas. B7-H3 expression on cancer cells is correlated with the number of T cells infiltrating the tumor. Endometrium tumor development and progression may be associated with downregulation of T-cell-mediated antitumor immunity through B7-H3.

Immunoexpression of PAX 8 in endometrial cancer: relation to high-grade carcinoma and p53.

PAX 8 is a crucial transcription factor for organogenesis of the thyroid gland, kidney, and the Müllerian system and plays an essential role in cell proliferation. The purpose of this study was to evaluate the association between p53 and PAX 8 expression and the clinical value of PAX 8 in endometrial carcinoma. We detected 106 consecutive patients with primary endometrial carcinoma (type I/ endometrioid, n=84; type II/ nonendometrioid, n=20; rare subtypes, n=2) who were treated at our institution between 1999 and 2009. Of the 106 patients, 97 cases were eligible for further investigations. PAX 8 and p53 expression were assessed using immunohistochemistry from paraffin-embedded tissue blocks. Results were correlated with clinical data. PAX 8 immunoreaction was found in 70 of 97 (72.1%) patients, including 56 of 77 (72.7%) endometrioid carcinomas and 13 of 18 (72.2%) type II carcinomas. A positive correlation was observed between PAX 8 and p53 expression (P=0.0005), histologic type (P=0.04), and histologic grade (P=0.02). No association was found between PAX 8 expression and tumor stage, vascular space involvement, lymph node involvement, and age of the patients. Furthermore, using univariate and multivariate analyses, no statistically significant relationship could be evaluated between patient survival data and PAX 8 expression. PAX 8 is expressed in the vast majority of endometrial carcinomas both of endometrioid and nonendometrioid type. PAX 8 overexpression correlates with p53 expression and high-grade endometrial carcinomas but seems not to be useful as a prognostic parameter.

immunohistochemical expression of survivin and γ-H2AX in vulvar intraepithelial neoplasia and low-stage squamous cell carcinoma.

Survivin inhibits apoptosis and is involved in the regulation of cell cycle progression and in the mitotic spindle formation. It is overexpressed in many cancers. The histone γ-H2AX is a marker of activated DNA damage and is overexpressed in different cancers and their precursor lesions. It also forms early during apoptosis. Eighty-seven formalin-fixed, paraffin-embedded archival vulvar tissues originating from 55 preoperatively untreated patients were immunostained with antibodies to survivin and γ-H2AX to determine their expression in normal squamous vulvar epithelia (NE, n=25), lichen sclerosus (n=10), high-grade classic vulvar intraepithelial neoplasia (n=16), differentiated vulvar intraepithelial neoplasia (n=16), and vulvar invasive keratinizing squamous cell carcinoma (ISCC, n=20; FIGO Ib). Immunostaining for both factors was scored for moderate and strong intensities with regard to quantity. Statistical analysis was performed by the χ test and Fisher exact test. Nuclear surviving expression increased from NE and lichen scleros to high-grade classic vulvar intraepithelial neoplasia, differentiated vulvar intraepithelial neoplasia, and ISCC significantly (P=0.0001) and followed the distribution of immature squamous epithelial cells. Positive scores for γ-H2AX were found in nuclei of cells in all diagnostic cohorts, in any epithelial level with some accentuation in the upper layers, was seen in pycnotic nuclei in horn pearls of ISCC and apoptotic bodies, without relevant statistical distributions. Immunoscores did not differ between grade 1 and grades 2/3. Expression patterns were different for both factors, suggesting their involvement in different biologic mechanisms as an early event leading to resistance to apoptosis in vulvar carcinogenesis.

Expression of γ-H2AX in endometrial carcinomas: an immunohistochemical study with p53.

OBJECTIVE.: The most frequently mutated gene in human cancer is p53, a gene that functions in the checkpoint response to DNA double-strand breaks. γ-H2AX is a marker of activated DNA damage and is overexpressed in many malignancies and their precursor lesions. The purpose of this study was to evaluate the association between p53 and γ-H2AX expression and the clinical value of γ-H2AX in endometrial carcinoma. METHODS.: We investigated 106 patients with primary endometrial carcinoma (type I/endometrioid, n=84; type II/non-endometrioid, n=20; mixed pattern or other histological types, n=2) who were treated at our institution between 1999 and 2009. γ-H2AX and p53 expression were assessed using immunohistochemistry from paraffin-embedded tissue blocks, and results were correlated with clinical data. RESULTS.: A strong positive correlation was observed between γ-H2AX and p53 expression (p<0.0001). Like p53, γ-H2AX staining was significantly associated with advanced tumor stage (p=0.04), histological grade (p<0.0001), histological type (p<0.0001), and vascular space involvement (p=0.05), but not with lymph node involvement (p=0.64) and patients' age (p=0.36). In a univariate survival analysis, p53 and γ-H2AX staining were associated with a shortened disease-free and overall survival but in the Cox regression analyses both parameters did not serve as independent prognostic parameter. CONCLUSIONS.: Our findings suggest that there is a link between the p53 dependent cell cycle arrest and γ-H2AX dependent DNA repair pathway in endometrial cancer. Increasing expression levels of γ-H2AX are associated with unfavourable prognostic factors in type I and type II endometrial carcinomas.

Expression of phosphorylated histone H2AX (γ-H2AX) in normal and neoplastic squamous epithelia of the uterine cervix: an immunohistochemical study with epidermal growth factor receptor.

The histone γ-H2AX is a marker of activated DNA damage and is overexpressed in different cancers and their precursor lesions, indicating a role in oncogenic transformation. Epidermal growth factor receptor (EGFR) is overexpressed in many kinds of epithelial neoplasms. This study aimed to determine whether immunohistochemical expression of γ-H2AX is involved in the progression of the morphological spectrum from normal squamous cervical epithelia (NE, n=33) to cervical intraepithelial neoplasia (CIN; CIN1, n=9; CIN2/3, n=33) and cervical invasive squamous cell carcinoma (ISCC, n=33), whether γ-H2AX expression follows the pattern of proliferation of atypical squamous cells as shown by EGFR immunoreactivity, and whether it is correlated with clinicopathologic variables in ISCC. Immunostaining for both the factors was scored semiquantitatively for moderate and strong intensities. Gamma-H2AX and EGFR expression, respectively, increased from NE and CIN1 to CIN2/3 and ISCCs significantly (P=0.0001, respectively). Gamma-H2AX reactivity was found in the nuclei of the cells of the upper epithelial levels and the cells of basal/parabasal type in variable quantities in NE and CIN; expression of γ-H2AX was seen in the nuclei of ISCC including keratinizing cells in horn pearls. EGFR staining was mainly membranous and noted in basal/parabasal cells in NE and atypically proliferating keratinocytes in CIN and nonkeratinizing cells of ISCC. In addition, immature squamous metaplasias were decorated by the antibodies used. Immunoscores for γ-H2AX and EGFR, respectively, did not differ between International Federation of Gynecology and Obstetrics stages I and II, keratinizing and nonkeratinizing ISCC, and CIN2/3 and ISCC. However, expression patterns were different for both the factors, suggesting their involvement in different biological mechanisms, with regard to γ-H2AX apart from proliferation. Overexpression of γ-H2AX in CIN2/3 and ISCC of the uterine cervix reflects the neoplastic transformation of cervical squamous epithelia in reaction to increased DNA-damage and supports the classification of dysplasia into low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions.

Undifferentiated Endometrial Sarcoma of the Ovary: A Case Report with Review of Recent Literature and Discussion of Lacking Specificity of CD10 Immunoreactivity.

Undifferentiated endometrial sarcomas (UESs) of the ovary are very rare tumors. This paper presents a case of a 56-year-old patient with a history of hysterectomy and bilateral salpingectomy seven years ago for uterine leiomyomata. Intraoperatively, a tumor originating from the left ovary, adherent to the sigmoid colon, with infiltration of the small intestine and the vaginal apex was found. Histologically, the tumor was composed of pleomorphic round and oval to spindled cells with polymorphous vesicular nuclei with coarse chromatin and large nucleoli. Mitotic activity was brisk. There were large necrotic areas. Adjacent to the tumor tissue endometrium-like glands surrounded by fibrous stroma with macrophages corresponding to ovarian endometriosis were noted. Tumor cells showed diffuse strong immunoreactivity for vimentin and patchy strong staining for CD10; no reactivities were found for AE1/AE3, desmin, S-100, LCA, CD20, c-kit, and CD31. The patient died of her neoplastic disease four months postoperatively. CD10 is frequently expressed in different gynecopathological as well as other lesions, and, thus, nonspecific without relevance to the classification of this case. Morphological features, extensive sampling, and appropriate immunohistochemistry including markers for cytokeratins and myogenic differentiation are mandatory to arrive at the correct diagnosis.

The accuracy of frozen section analysis in ultrasound- guided core needle biopsy of breast lesions.

BACKGROUND: Limited data are available to evaluate the accuracy of frozen section analysis and ultrasound- guided core needle biopsy of the breast. METHODS: In a retrospective analysis data of 120 consecutive handheldultrasound- guided 14- gauge automated core needle biopsies (CNB) in 109 consecutive patients with breast lesions between 2006 and 2007 were evaluated. RESULTS: In our outpatient clinic120 CNB were performed. In 59/120 (49.2%) cases we compared histological diagnosis on frozen sections with those on paraffin sections of CNB and finally with the result of open biopsy. Of the cases 42/59 (71.2%) were proved to be malignant and 17/59 (28.8%) to be benign in the definitive histology. 2/59 (3.3%) biopsies had a false negative frozen section result. No false positive results of the intraoperative frozen section analysis were obtained, resulting in a sensitivity, specificity and positive predicting value (PPV) and negative predicting value (NPV) of 95%, 100%, 100% and 90%, respectively. Histological and morphobiological parameters did not show up relevance for correct frozen section analysis. In cases of malignancy time between diagnosis and definitive treatment could not be reduced due to frozen section analysis. CONCLUSION: The frozen section analysis of suspect breast lesions performed by CNB displays good sensitivity/specificity characteristics. Immediate investigations of CNB is an accurate diagnostic tool and an important step in reducing psychological strain by minimizing the period of uncertainty in patients with breast tumor.

Nucleoporin 88 expression in normal and neoplastic squamous epithelia of the uterine cervix.

This study investigated the expression of nucleoporin 88 (Nup88) in formalin-fixed, paraffin-embedded archival tissues of cervical specimens consisting of normal ectocervical squamous epithelia (n = 34), low-grade squamous intraepithelial lesions corresponding to cervical intraepithelial neoplasia (CIN) 1 (n = 9), high-grade squamous intraepithelial lesions corresponding to CIN2 and CIN3 (n = 28), and invasive squamous cell carcinoma (ISCC; n = 30) to determine whether expression of this factor is involved in the progression of the morphological spectrum from normal cervical epithelia to CIN and cervical ISCC. A standard immunohistochemical technique was performed using a Ventana BenchMark XT immunostainer with a mouse antihuman monoclonal antibody to Nup88. Immunostaining was scored with regard to quantity and intensity of positively stained cells, with final immunoscores from 0 to 12 in each case. Nucleoporin 88 immunoscores increased significantly from normal ectocervical squamous epithelia to CIN1, CIN2/3, and ISCC (P < .0001, analysis of variance). Cervical intraepithelial neoplasia 2/3 as isolated lesions and adjacent to ISCC did not differ significantly. A significant correlation was noticed for immunoscores of CIN2/3 adjacent to ISCC and the corresponding ISCC (P = .0007). This study indicates that Nup88 is significantly overexpressed in high-grade CIN lesions and ISCC compared with normal ectocervical squamous epithelia and CIN1. However, Nup88 evaluation is of limited value as a diagnostic marker in individual cases.

Epidermal growth factor receptor expression in serous ovarian carcinoma: an immunohistochemical study with galectin-3 and cyclin D1 and outcome.

This study investigated the expression of epidermal growth factor receptor (EGFR), galectin-3 and cyclin D1 in a cohort of ovarian serous carcinomas with regard to outcome and clinicopathologic parameters. Formalin-fixed paraffin-embedded archival tissues of fifty ovarian serous carcinomas were stained with anti-bodies to EGFR, Gal-3, and cyclin D1 by automated immunohistochemistry. Additionally, 10 benign serous cystadenomas and 10 typical serous borderline ovarian tumors were included in the study. Immunostaining was scored with regard to quantity and intensity of positively stained nuclei. Staining patterns were recorded. The EGFR expression was scored negative in all serous cystadenomas and serous borderline ovarian tumors. Membranous and cytoplasmic EGFR immunoreactivity was determined in 64% of ovarian serous carcinomas; it was related to high grade (P=0.0005) and poor outcome (P=0.0137) but not with stage (P=0.5118). Galectin-3 and cyclin D1 immunostaining decreased from serous cystadenomas and serous borderline ovarian tumors to the carcinomas significantly (P=0.0022 and P=0.0083, respectively). Galectin-3 immunostaining of any pattern (nuclear and cytoplasmic as well as merely cytoplasmic taken together) was not related to grade or stage in cancers; mere cytoplasmic expression was associated with poor outcome (P=0.0097). Cyclin D1 immunoreactivity in predominantly nuclear pattern was increased in low-grade carcinomas (P=0.0378) but was not related to stage and outcome (P=0.6578 and P=0.0675, respectively). This study indicates that with regard to EGFR and cytoplasmic galectin-3 immunoexpression, multiple marker testing may be an adjunct in the identification of high-risk ovarian serous cancers.

Symptomatic large bowel endometriosis in a woman with a hormonal intrauterine device: a case report.

BACKGROUND: Extragenital endometriosis can occur in the rectum and sigmoid causing cyclic rectal bleeding. A hormonal intrauterine device (IUD) (20 microg/24 h levonorgestrel releasing), originally developed as an easily reversible contraceptive method, is a therapeutic option for bleeding disorders. CASE: A 34-year-old woman using depot progesterone injection (crys-talline suspension of 150 mg medroxyprogesterone acetate) for contraception was amenorrheic and asymptomatic. After switching to a levonorgestrel-releasing IUD the patient experienced irregular bleeding with concomitant dysmenorrhea and rectal bleeding. Colonoscopy revealed a sigmoid mass. Laparotomy with resection of the sigmoidal mass and ovarian cyst was performed. Histopathologic analysis confirmed the suspected diagnosis of large bowel endometriosis. CONCLUSION: In our patient, large bowel endometriosis became symptomatic 2 years after insertion of hormonal IUD. The suppressive effect of the hormonal IUD seemed to be insufficient for the control of extragenital endometriosis.

Epidermal growth factor receptor is involved in the development of an invasive phenotype in vulvar squamous lesions, but is not related to MIB-1 immunoreactivity.

This study investigated the expression of epidermal growth factor receptor (EGFR) and proliferation as determined by MIB-1 labeling indices (proliferation index [PI]) in 82 cases of vulvar tissues consisting of healthy epithelia (HE) (n = 10), vulvar condylomas (VC; n = 24), high-grade vulvar intraepithelial neoplasias (HG-VIN) of warty and basaloid types (n = 26), invasive keratinizing squamous cell carcinomas (SCCs; n = 22), and differentiated VIN adjacent to SCCs (n = 7) by means of a standard immunohistochemical method using monoclonal antibodies to characterize EGFR expression, with an emphasis on neoplastic transformation and progression, and to relate it to proliferation. The EGFR expression was mainly membranous and--to a lesser degree--cytoplasmic; it was scored for intensity and quantity. The MIB-1 reactivity was exclusively nuclear. High EGFR immunoscores were detected on 6% of HG-VIN and 41% of SCCs. The EGFR immunoexpression increased significantly from healthy epithelia to VCs, VINs (HG-VIN and differentiated VIN taken together), and SCCs (P < 0.0001 [chi2 test]), but was not related to stage, grade, or recurrence in SCCs. There was no statistical significance for EGFR immunoscores and PIs in the groups of VCs (P = 0.1923), VINs (P = 0.0951), and SCCs (P = 0.6896). This study shows the upregulation of EGFR expression in a few warty and basaloid HG-VIN cases and in many SCCs of the vulva. The lack of a relationship with PIs suggests that mechanisms other than proliferation are involved in this process.

Poly(adenosine diphosphate-ribose) polymerase expression in serous ovarian carcinoma: correlation with p53, MIB-1, and outcome.

This study investigated the expression of poly(adenosine diphosphate-ribose) polymerase (PARP) in a cohort of ovarian serous carcinomas by immunohistochemistry with regard to outcome, clinicopathologic parameters, proliferation as assessed by MIB-1 labeling indices (LIs), and p53 immunoexpression. Formalin-fixed, paraffin-embedded archival tissues of 50 ovarian serous carcinomas were immunostained with antibodies to PARP, MIB-1, and p53. In addition, 10 benign serous cystadenomas and 10 typical serous borderline ovarian tumors were included in the PARP immunostudy. Immunostaining for PARP was scored with regard to quantity and intensity of positively stained nuclei as negative, low, or strong. The MIB-1 LIs were quantitated as the percentage of positively stained nuclei in 1000 nuclei. For p53, at least 10% of tumor cells had to display nuclear staining. The expression of PARP was scored negative in all serous cystadenomas and low in serous borderline ovarian tumors. Strong PARP expression was determined in 38 cases (76%), and low expression in 12 cases (12%) of ovarian serous carcinomas; MIB-1 staining was noted in all cases (mean, 44.2; range, 10.8-66.5), positivity for p53 in 39 cases (78%). The PARP immunoreactivity increased with the International Federation of Gynecology and Obstetrics stage (P = 0.0075), as well as p53 positivity (P = 0.0141) and MIB-1 LIs (P = 0.0102), with grade determined after Malpica et al. (P = 0.0445) but not with grade assessed after Shimizu et al. (P = 0.1495). A trend for poor outcome was observed in patients whose tumors displayed high levels of PARP immunoexpression (P = 0.0196, log-rank test). This study indicates that PARP expression is frequently upregulated in ovarian serous carcinomas, related with MIB-1 LIs and p53 expression, and may serve as a marker of aggressive behavior with prognostic value.