Sigrid Regauer

Medical University of Graz, Gratz, Styria, Austria

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Publications (102)286.69 Total impact

  • Olaf Reich, Sigrid Regauer
    American Journal of Surgical Pathology 09/2014; · 4.87 Impact Factor
  • Sigrid Regauer, Olaf Reich, Barbara Eberz
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    ABSTRACT: Vulvar squamous cell carcinomas (SCCs) arising in association with vulvar lichen planus (LP) are poorly documented.
    Journal of the American Academy of Dermatology 07/2014; · 4.91 Impact Factor
  • Olaf Reich, Sigrid Regauer
    International Journal of Cancer 07/2014; · 6.20 Impact Factor
  • Sigrid Regauer, Christine Beham-Schmid
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    ABSTRACT: Introduction. Lichen planus (LP) is a chronic cytokine-mediated disease of possible auto-immune etiology. 25% of men have anogenital manifestations. Erosive penile LP causes a scarring phimosis of the foreskin in uncircumcised men. Mast cells as potent immune modulators have been implicated in a number of autoimmune and chronic inflammatory diseases, but have not been investigated in LP. Material and Methods. Formalin-fixed tissues of 117 circumcision specimens of adult men affected by LP were evaluated for the extent of mast cell and lymphocyte infiltrates, characterized immunohistochemically with antibodies to CD 3,4,8,20,21,25,30,117c and human mast cell tryptase. Specimens with dense mast cell infiltrates were analyzed for point mutations of the c-kit gene (D816V). Results Unaffected skin and modified mucosa of foreskins contained ⟨5 mast cells/mm². The inflammatory infiltrate of LP-lesions displayed ⟨15 mast cells/mm² in 33/117 foreskins, 16-40 mast cells/mm2 in 22/117 and ⟩40 mast cells/mm² (average 70, range 40-100) in 62/117 foreskins. Lesional mast cells of 29/117 (24%) foreskins showed aberrant CD25-expression and/or spindled morphology, with 11/29 men having erosive LP, 13/29 a lymphocytic vasculitis and 1/28 a systemic mastocytosis. Neither CD30-expression nor c-kit mutations were identified. Atypical mast cell infiltrates in LP correlated with high disease activity, erosive LP and presence of lymphocytic vasculitis Conclusions Increased mast cells in penile LP, mostly representing a benign hyperplasia/activation syndrome, suggests them as targets for innovative therapy options for symptomatic LP-patients not responding to corticosteroid therapy. Presently, the biological implications of atypical mast cell infiltrates in penile LP are unknown.
    Histology and histopathology 01/2014; · 2.28 Impact Factor
  • Source
    Sigrid Regauer, Olaf Reich, Barbara Eberz
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    ABSTRACT: Background Vulvar squamous cell carcinomas (SCCs) arising in association with vulvar lichen planus (LP) are poorly documented. Objectives We sought to present clinicopathological features of 38 patients (median age 61 years, range 39-90 years) with LP-associated vulvar SCCs. Methods Evaluated were location of vulvar SCC and metastases at presentation, recurrences, survival, precursor lesions, presence of human papillomavirus DNA, p16ink4a, and p53 expression. Results In all, 32 solitary (5 pT1a, 20 pT1b, 7 pT2) and 6 multifocal SCCs, located in the vestibulum (n = 20) and in nonhair-bearing modified and glycogenated mucosa (n = 18), arose in erosive (n = 13) and nonerosive (n = 25) LP. All SCCs were human papillomavirus DNA and p16ink4a negative. Sixteen of 38 (42%) women had inguinal metastases at presentation. Treatment was surgery with clear margins (36/38) and chemoradiation (2/38). Fourteen of 36 (39%) surgically treated patients developed between 1 and 5 new SCCs in the residual diseased mucosa. Of all recurrences, 68% developed within 12 months via precursors revealing various histologic features including elongated, but also flat rete ridges, basaloid and hypertrophic differentiation with inconsistent p53 expression. Fourteen of 38 (37%) patients died of SCCs. Limitations Retrospective study and lack of a standardized treatment protocols are limitations. Conclusion LP-associated SCCs were located in nonhair-bearing vulvar mucosa. Patients had a high rate of inguinal metastases, recurrent vulvar cancers in diseased mucosa, and disease-related death.
    Journal of the American Academy of Dermatology 01/2014; · 4.91 Impact Factor
  • Sigrid Regauer, Olaf Reich
    Gynecologic Oncology 07/2013; · 3.93 Impact Factor
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    ABSTRACT: BACKGROUND: Penile squamous cell carcinomas (SCC) arise either through transforming infections with human papillomavirus (HPV) or independent of HPV, often in the background of lichen sclerosus (LS) and lichen planus (LP). Despite impact on therapy and prognosis, etiologic stratifications are missing in most histological diagnoses and publications about penile cancers/precursors. OBJECTIVE: Classification of penile lesions into HPV-induced or HPV-negative via immunohistochemical demonstration of p16ink4a overexpression, a surrogate marker for transforming HPV-high-risk infections, and p53 expression in the absence of p16ink4a overexpression. METHODS: Archival formalin-fixed material of 123 invasive penile cancers and 43 pre-invasive lesions was evaluated for the presence of LS, LP, 28 HPV genotypes, and expression of p53 and p16ink4a. RESULTS: Seventy-two of 123 SCCs and 33 of 43 pre-invasive lesions showed p16ink4a overexpression independent of HPV-HR genotypes involved; 66 of 72 SCCs and 29 of 43 precursor lesions revealed a single HPV-high-risk-genotype (HPV-HR16 in 76% followed by HPV33, HPV31, HPV45, HPV18, HPV56); 5 of 72 SCCs and 4 of 43 precursor lesions revealed multiple HPV-HR-genotypes. One SCC revealed HPV-LR and HR-DNA. Fifty-one of 123 SCCs and 10 precursor lesions were p16ink4a negative, but showed nuclear p53 expression in tumor cells and basal keratinocytes. Forty-nine of 51 SCCs and 10 of 10 precursor lesions lacked HPV DNA. Two of 51 SCCs contained HPV18 and HPV45 DNA, respectively, but p16ink4a negativity classified them as non-HPV-induced. Twenty-seven of 51 SCCs showed peritumoral LS, 13 of 51 SCCs showed peritumoral LP, and 11 SCCs revealed no peritumoral tissue. Histologically, HPV-negative precursors showed hyperkeratotic, verrucous, atrophic, and basaloid differentiation. LIMITATIONS: This was a retrospective study. CONCLUSIONS: p16ink4a overexpression identifies HPV-HR-induced penile carcinogenesis independent of HPV-HR genotype. p53 expression along with p16ink4a negativity identifies HPV-negative cancers. Correct etiologic classification of penile lesions during diagnostic work-up allows optimal therapy decisions.
    Journal of the American Academy of Dermatology 03/2013; · 4.91 Impact Factor
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    ABSTRACT: Background: Elastofibroma dorsi is a benign soft tissue lesion composed of abnormal elastic fibers. Degenerated elastic fibers in skin and liver are associated with clusterin, an apoprotein that shares functional properties with small heat shock proteins. We evaluated the staining pattern and possible role of clusterin in elastofibroma dorsi. Material and methods: Twenty-one subcutaneous elastofibromas from the scapular region were evaluated with Elastica van Gieson and Orcein stains, immunohistochemically with antibodies to clusterin, smooth muscle actin, S-100, vimentin and CD34 and correlated with clinical data with respect to physical trauma. Results: Clusterin correlated with the staining pattern of Elastica van Gieson and labelled abnormal broad coarse fibrillar and globular elastic fibers in all elastofibromas. Orcein stains additionally identified fine oxytalan fibers which were not stained by clusterin. Clusterin staining was observed only on the outside of the elastin fibers, while the cores of fibers and globules were unstained. 4/21 elastofibromas showed cellular nodules with a myxoid/ collagenous stroma. The round to oval cells showed cytoplasmic staining with vimentin and clusterin; CD34 labelled mostly cell membranes. The cells lacked SMA and S-100 expression. The central areas of the nodules were devoid of elastic fibers, but the periphery contained coarse fibers and globules. 9/ 11 patients, for whom clinical data were available, reported trauma to the scapular region. Conclusion: Many investigated ED were associated with trauma, which supports a reactive/ degenerative etiology of ED. The abnormal large elastic fibers in all ED were enveloped by clusterin. Clusterin deposition may protect elastic fibers from degradation and thus contribute indirectly to the tumor-like presentation of ED.
    Histology and histopathology 01/2013; · 2.28 Impact Factor
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    ABSTRACT: OBJECTIVE: Prediction of lymph node (LN) metastases in penile invasive cancer relies on clinical features and histologic characteristics of the primary tumor. Correct prediction, however, is difficult, as only 50% patients undergoing lymphadenectomies will have LN metastases. In 2009, the tumor, nodes, metastases (TNM) classification for staging of early penile cancers was revised. We tested the predictive accuracy of the revised TNM classification in a low incidence area for penile carcinoma. MATERIALS AND METHODS: The presence of LN metastases in 76 men with pT1 penile cancers was correlated with the 2009 TNM subclassification, which is based on a combined evaluation of tumor grade and lymphatic invasion, but also with individual parameters, such as histologic grade, lymphatic invasion, perineural invasion, invasion depth, growth pattern and human papilloma virus (HPV) status. RESULTS: 76pT1 penile cancers were reclassified into 31pT1a squamous cell carcinomas (SCC) and 45pT1b (41 SCC; 4 clear-cell carcinomas); 12/22 men (55%; 8 SCC, 4 clear-cell carcinomas) undergoing lymphadenectomy for enlarged inguinal lymph nodes had metastases, 54 patients without enlarged LN and lymphadenectomies had no LN metastases during follow-up of median 47 months. Statistically, clear cell differentiation of the primary carcinoma was highly associated with metastases (100% clear-cell carcinomas vs. 11% SCC) and poor survival (50% vs. 5.5%). Among conventional SCC, only lymphatic invasion showed a highly significant association with metastases with 100% specificity. The 2009 TNM classification, tumor grade alone, perineural invasion, growth pattern, invasion depth or HPV status could not predict LN status. Lymphadenectomy for enlarged LN resulted in 100% sensitivity and 42% predictive probability for identifying metastases and a 16% false positive rate. Statistically, survival correlated significantly with clear-cell differentiation and with lymphatic invasion in both clear-cell carcinomas and conventional SCC. CONCLUSIONS: Penile clear-cell carcinomas are more aggressive cancers than SCC. Our observation suggests a benefit of a prophylactic lymphadenectomy for patients with clear-cell carcinomas. Among conventional SCC, only lymphatic invasion predicted LN metastases. Neither tumor grade alone nor perineural invasion, growth pattern, depth of invasion, and subgrouping according to the revised TNM classification correlated with metastases. Clinical evaluation of the LN status was superior to histologic risk stratification.
    Urologic Oncology 03/2012; · 3.65 Impact Factor
  • Olaf Reich, Sigrid Regauer
    American journal of obstetrics and gynecology 11/2011; 206(3):e11; author reply e11-2. · 3.28 Impact Factor
  • Sigrid Regauer
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    ABSTRACT: Despite the strong association of lichen sclerosus (LS) and vulvar squamous cell carcinoma (SCC), the role of LS as precancerous lesion is unclear and the risk for recurrent SCC in residual LS after surgery for a LS-associated SCC is unknown. Recurrences in residual vulvar LS after complete resection of a LS-associated SCC were analyzed in 75 women. Primary SCC, recurrences and 19 biopsies obtained 1-6 months before recurrent SCC were evaluated histologically, and for presence of HPV and monoclonally rearranged T-cell receptor gamma locus (mTRG@). 40/75 patients (53%; primary SCC 25pT2, 9pT1b, 6pT1a) had no recurrence for 64 months (range 10-176 months), but 35/75 women (47%; primary SCC 1pT3, 18pT2, 13pT1b, 3pT1a) developed recurrences after 42 months (range 3-156 months). Twenty-five women had 1 recurrence: 13SCC within 18 months, 1SCC after 26 months, 10SCC and 1 differentiated vulvar intraepithelial neoplasia (d-VIN) after 74 months (range 52-136 months). Ten patients suffered multiple recurrences: 3 women had 2 recurrent d-VIN, 7 patients had multiple successive de-novo SCC with lymphocytes with mTRG@ in 6 patients. Wider resections correlated with no/late recurrences. Nineteen HPV-negative biopsies before diagnosis of recurrent SCC revealed 4 classical d-VIN and 15 verrucous, atrophic or flat intraepithelial proliferations different from d-VIN. With a 50% recurrence rate after cancer surgery, residual anogenital LS has a high risk for de-novo cancer. Extent of resection of LS-affected skin and activity of residual LS with lymphocytes with mTRG@ are important criteria for recurrences, which develop rapidly through a variety of HPV-negative intraepithelial lesions.
    Gynecologic Oncology 07/2011; 123(2):289-94. · 3.93 Impact Factor
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    ABSTRACT: Human papillomavirus (HPV) infections account worldwide for 50% of penile cancers. The role of lichen sclerosus and lichen planus in penile carcinogenesis needs further investigation. Archival formalin-fixed high-grade penile intraepithelial neoplasias, differentiated penile intraepithelial neoplasias, and invasive carcinomas from a single pathology institution in a low-incidence area for penile cancer were analyzed for 28 HPV low-risk and HPV high-risk genotypes, p16 overexpression, presence of peritumoral lichen sclerosus, lichen planus, precursor lesions, and monoclonal rearrangement of the T-cell receptor γ locus. A total of 29 penile intraepithelial neoplasias (100%) and 69 of 115 (60%) invasive cancers contained HPV high-risk genotypes with a single HPV high-risk genotype (80% HPV16, 6% HPV33, 2% HPV45 and HPV18, 1% HPV73). Multiple HPV high-risk genotypes were identified in 4% with and in 5% without HPV16/18. p16 overexpression correlated in all but 1 case of HPV high-risk 45 cancer. No p16 overexpression and HPV genotype was found in 6 differentiated penile intraepithelial neoplasias and 46 of 115 (40%) invasive cancers, 30% of which were pT2/pT3 cancers. For 35 cancers, peritumoral tissue was available for analysis. Advanced lichen sclerosus was identified in 26, lichen planus in 9, and differentiated penile intraepithelial neoplasia in 18 carcinomas. Dense T-cell-dominant lymphocytic infiltrates were identified in 22 of 46 carcinomas and in 3 of 6 differentiated penile intraepithelial neoplasias, with 6 of 13 analyzed carcinomas/penile intraepithelial neoplasias showing a monoclonal rearrangement of the T-cell receptor γ locus. The prevalence of HPV high-risk in penile cancers from a low-incidence area was slightly higher than the global distribution. HPV-negative carcinomas were associated with advanced lichen sclerosus and lichen planus, differentiated penile intraepithelial neoplasia, and accumulation of T lymphocytes with monoclonal rearrangement of the T-cell receptor γ locus.
    The American journal of surgical pathology 07/2011; 35(7):998-1006. · 4.06 Impact Factor
  • Journal of Clinical Oncology 04/2011; 29(17):e506-8. · 18.04 Impact Factor
  • Journal of the European Academy of Dermatology and Venereology 03/2011; 25(3):369-70. · 2.69 Impact Factor
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    ABSTRACT: Low-grade endometrial stromal sacomas (ESS) are estrogen-sensitive tumors. Polymorphic variation in the CYP19 gene can affect estrogen synthesis by increasing aromatase activity resulting in elevated levels of estrone and estradiol. We examined the polymorphism 1558 C > T in he aromatase gene (CYP19A1) in a series of 20 low-grade endometrial stromal sarcomas. Archival formalinfixed and paraffin-embedded material was analyzed with a fast real-time PCR system. The homozygous C/T- and the homozygous mutant T/T-genotypes were detected in 10/20 (50%) and 7/20 (35%) samples, respectively. Polymorphism 1558 C > T in the aromatase gene may represent a high-risk allele with increased local estrogen levels.
    European journal of gynaecological oncology 01/2011; 32(6):626-7. · 0.58 Impact Factor
  • S Regauer, B Eberz
    British Journal of Dermatology 09/2010; 163(3):663-5; author reply 665-6. · 3.76 Impact Factor
  • Source
    B Eberz, S Regauer
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    ABSTRACT: mit LS ein Screening auf TPO- und TG-Antikör- per. Bei erhöhten Titern sollte eine Abklärung mittels Schilddrüsensonogramm sowie eine Be- stimmung von basalem "thyroid-stimulating hormone" (TSH), freiem T3 und freiem T4 erfol- gen. In der Schilddrüsensprechstunde sollten Frauen mit Hashimoto-Thyreoiditis gezielt nach chronischen bzw. rezidivierenden anogenitalen Beschwerden, insbesondere Pruritus, Brennen oder Dyspareunie befragt werden. Bei positiver Anamnese ist eine Zuweisung an einen auf Vulvaerkrankungen spezialisierten Facharzt für Gynäkologie sinnvoll. Abstract: Concomitant Occurrence of Lichen Sclerosus and Hashimoto's Thyroiditis. Lichen sclerosus (LS) is a chronic inflammatory skin dis- ease with an immune dysregulation as the un- derlying cause. As of June 1, 2009, 278/3040 patients of a practicing gynecological physician in Mürzzuschlag had a clinically and biopsy- proven anogenital LS, commensurate with a prevalence of 9.1 %. The standard procedure of obtaining skin biopsies in patients with chronic vulvar symptoms allowed the detection of early stages of LS. Every patient with an initial diag- nosis of LS in this practice undergoes routine serological screening for autoantibodies follow- ing the "Guidelines for the Management of Li- chen Sclerosus" (1). In 263/278 of our LS pa- tients, a serological screening for autoimmune diseases was performed. Pathological eleva- tions of autoantibodies to thyroglobulin (TG) and/or thyroid peroxidase (TPO) were found in 58/263 LS patients (23 %). In 50/263 (19 %) of our LS patients, Hashimoto's thyroiditis was confirmed by sonography of the thyroid gland. 25 of these 50 LS patients with Hashimoto's thy- roiditis (50 %) had a prior diagnosis and were known to be hypothyroid. In the other 50 % (25 patients!), however, the primary diagnosis of Hashimoto's thyroiditis was made only after se- rological screening during the routine workup for a diagnosis of vulvar LS. Due to the high per- centage of occult Hashimoto's thyroiditis in LS patients, we recommend a screening for TPO and TG autoantibodies in all patients with vulvar LS. Pathological elevation of one or both values should be followed by sonography of the thyroid gland and serological analysis of basal TSH, free T3, and T4. Specialists in thyroid disease should be aware of the strong association of thyroid disease and anogenital LS. Women with a diagnosis of Hashimoto's thyroiditis should be questioned specifically for chronic vulvar symp- toms, in particular for pruritus, burning pain, and dyspareunia. In case of a positive history, pa- tients should be referred for further evaluation to a gynecologist with experience in vulvar dis- eases. J Klin Endokrinol Stoffw 2009; 2 (3): 7-10.
    Geburtshilfe Und Frauenheilkunde - GEBURTSH FRAUENHEILK. 01/2010; 70(05).
  • O Reich, S Regauer, S Scharf
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    ABSTRACT: Endometrial stromal sarcomas (ESS) are rare uterine tumors with unknown etiological risk factors, but estrogen-dependent growth promotion. We present two patients with advanced ESS, who had increased levels of p,p-DDE; hexachlorobenzene; PCB 28; PCB 52; PCB 101; PCB 138; PCB 153 and PCB 180 in abdominal adipose tissue. Other xenoestrogens were within expected limits for the non-exposed European population. Increased levels of xenoestrogens in patients with ESS may be involved in the pathogenesis of ESS. Chronic exposure to xenoestrogens may be a risk factor for tumor progression.
    European journal of gynaecological oncology 01/2010; 31(1):105-6. · 0.58 Impact Factor
  • Geburtshilfe Und Frauenheilkunde - GEBURTSH FRAUENHEILK. 01/2010; 70(05):374-378.
  • B Eberz, S Regauer
    Geburtshilfe und Frauenheilkunde 09/2009; 69(09). · 0.85 Impact Factor

Publication Stats

971 Citations
286.69 Total Impact Points

Institutions

  • 1998–2014
    • Medical University of Graz
      • Institute of Pathology
      Gratz, Styria, Austria
    • Elisabethinen Hospital
      Linz, Upper Austria, Austria
  • 2009
    • Samsun Kadın Doğum ve Çocuk Hastalıkları Hastanesi
      Djanik, Samsun, Turkey
  • 1999–2007
    • Karl-Franzens-Universität Graz
      • Institute of Psychology
      Gratz, Styria, Austria
  • 2006
    • National Maternity Hospital
      Dublin, Leinster, Ireland
  • 1997
    • IST Austria
      Klosterneuberg, Lower Austria, Austria