The Relationship of p53 Accumulation and DNA Ploidy and Conventional Clinicopathological Prognostic Variables in Patients with Ovarian Carcinoma

Osmanağaoğlu, Mehmet A.; Kadioglu, Salih Zeki; Osmanagaoglu, Selen; Bozkaya, Hasan

doi:10.1055/s-2005-865945

Cited by 13 publications

(21 citation statements)

References 27 publications

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“…Correlation of ploidy with endometrioid and non-endometrioid subtypes have been reported previously. 13 In this study we have confirmed this and further demonstrated the relation of ploidy and ploidy-related parameters with individual histologic subtypes. The present study differs from former ones in the use of high-resolution DNA ploidy histogram in which a larger number of nuclei are analyzed with simultaneous morphological observation of all nuclei.…”

Section: Discussionsupporting

confidence: 83%

“…10 DNA ploidy-related parameters such as DNA index, 8,11 percentage of cells exceeding 5c (5c ER) also provide prognostic information. 12 In the majority of DNA ploidy studies flow cytometry has been used on paraffin-embedded material [13][14][15][16] or frozen material. [17][18][19] The advantage is the analysis of 20 000-50 000 nuclei.…”

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confidence: 99%

“…9,13,15 Serous adenocarcinoma and clear cell adenocarcinoma are aggressive tumors 21 and are usually aneuploid. 11 Grade 1 endometrioid adenocarcinoma has better survival 21 and is usually diploid.…”

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confidence: 99%

“…11 Grade 1 endometrioid adenocarcinoma has better survival 21 and is usually diploid. 13 The reviewed diagnosis has been reported to better correlate with survival compared to routine typing and grading. 22 No comprehensive study comparing DNA ploidy with subtype and grade of endometrial carcinoma has been performed.…”

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Image cytometry DNA ploidy correlates with histological subtypes in endometrial carcinomas

et al. 2006

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Image cytometric DNA ploidy analysis of endometrial carcinomas was performed to determine whether ploidy status and ploidy-related parameters like DNA index, percentage of cells exceeding 5c and 9c, correlate with histologic subtype. This is a prospective study of 391 patients with stage I endometrial carcinoma which included 331 (85%) endometrioid adenocarcinoma, 22 (6%) serous adenocarcinoma, 7 (2%) clear cell adenocarcinoma, 2 (0.5%) small cell carcinoma, 1 (0.3%) undifferentiated carcinoma, and 28 (7%) unclassifiable adenocarcinoma. Twenty-five percent of endometrioid adenocarcinomas were non-diploid. In contrast, all clear cell adenocarcinomas and 21/22 (95%) of serous adenocarcinomas were non-diploid. Hyperdiploidy (25 cases) was found only in endometrioid adenocarcinomas. Mean DNA index of the stemline in serous adenocarcinoma (1.72) and clear cell adenocarcinoma (1.81) was higher than in endometrioid adenocarcinoma (1.1). The difference in ploidy-related parameters between endometrioid adenocarcinoma and serous adenocarcinoma was highly significant (Po0.001). In addition, Grade 3 endometrioid adenocarcinoma showed significant difference in all ploidy-related parameters compared with grade 1 and grade 2 tumors (Po0.001). Our results show that DNA ploidy-related parameters may be valuable in subtyping histologically difficult cases of endometrial carcinomas.

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Section: Discussionsupporting

confidence: 83%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Image cytometry DNA ploidy correlates with histological subtypes in endometrial carcinomas

et al. 2006

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“…11 The relative roles of both nuclear atypia and p53 positivity as independent (of each other) prognostic markers is controversial, due in part to the fact that the two are so closely linked to serous carcinoma. 12,13 However, investigators have verified the existence of p53-positive tumors with an endometrioid pattern, and in one study, p53 emerged as an important prognostic marker in this subset.…”

Section: Discussionmentioning

confidence: 99%

Histologic and immunohistochemical decision-making in endometrial adenocarcinoma

et al. 2008

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Diffuse p53 immunostaining distinguishes 85% of serous (Type II) from endometrioid (Type I) carcinomas and is an independent marker for poor prognosis. Interobserver reproducibility for the diagnosis of these entities, as well as selection and prediction of p53 immunostaining results, is unknown. Reproducibility of three pathologists regarding: (1) a two (I and II) and (2) three part classification (I, II or indeterminate); (3) recommendation for p53 staining and (4) expectations of p53 staining results were computed with the kappa (k) statistic. All cases were immunostained for p53 and independently scored. A two and three tiered classification scheme achieved high (k ¼ 0.71) and moderate (k ¼ 0.49) reproducibility. Non-unanimous cases were more likely to be reclassified into an 'indeterminate' category (27 cases, 39% of passes) compared to those with unanimous (82 cases, 14% of passes) classification. Pathologists recommended p53 immunostaining with poor (k ¼ 0.28) reproducibility, but staining prediction was made with good concordance (69%, k ¼ 0.50). Moreover, p53 staining was more common in diagnostically discordant (46%) compared to concordant (16%) cases. A subset of endometrial cancers do not readily fit within a two-class system and can be culled from cases that (1) do not achieve interobserver concordance and (2) are more likely to be chosen for p53 immunostaining and (3) are more likely to stain positive for p53. Because p53 is an important marker for endometrial adenocarcinoma outcome, and cannot be predicted in advance in indeterminate cases, p53 immunostaining should be employed in cases with observer disagreement in a binary system. Keywords: p53; endometrial neoplasms; serous carcinoma; reproducibility Endometrial adenocarcinoma is a biologically diverse disease that has been divided into two subgroups based on histomorphology, biologic behavior, and underlying genetic aberrations. Type I tumors exhibit endometrioid morphology, arise in the setting of increased estrogen exposure with subsequent development of precancerous lesions (endometrial intraepithelial hyperplasia-EIN/atypical hyperplasia), are associated with frequent PTEN inactivation mutations, and have a favorable outcome. 1,2 By contrast, Type II tumors demonstrate papillary serous or clear cell morphology, are not associated with any known precursor lesions, demonstrate frequent p53 mutations, and are associated with a poor outcome. 3,4 The differences between these groups are summarized in Table 1. The observation that uterine papillary serous carcinomas have a greater tendency to metastasis and/ or recurrence in the peritoneum underscores the importance of accurate diagnosis. 5 Although the distinction between serous and endometrioid subgroups of endometrial cancer has a strong theoretical basis, subsets of endometrial adenocarcinoma have been recognized that do not fall cleanly into either of the two categories. Tumors with glandular architecture that more closely approximate endometrioid adenocarcinoma may occasionally demonstrate...

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Zweites Rezidiv eines Granulosazelltumors mit verändertem Wachstumsmuster, erhöhter Mitoserate und Proliferationsindex

Engert¹,

Völker²,

Dietl³

2006

Geburtsh Frauenheilk

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EinleitungGranulosazelltumoren des Ovars gehören zur Gruppe der Stromazelltumoren und sind mit einer Inzidenz von 2 -3 % aller Ovarialtumoren eher selten. Zur histopathologischen Diagnosesicherung werden das charakteristische Wachstumsmuster dieser Tumoren sowie bestimmte immunhistochemische Färbungen herangezogen. Therapie der Wahl bei Erstdiagnose ist bislang die abdominale Hysterektomie und beidseitige Adnexektomie. Hinsichtlich einer adjuvanten Therapie besteht derzeit noch kein einheitlicher Consensus. Granulosazelltumoren rezidivieren in 9 -20% aller Fälle nach durchschnittlich 5 -10 Jahren. Dabei sind als Risikofaktoren für ein Rezidiv bislang Differenzierungsgrad, Mitoseindex und Tumorgröße anzusehen. ZusammenfassungBei unserer Patientin traten im Zeitraum von sieben Jahren zweimalig rezidivierend Granulosazelltumoren auf, die zunächst jeweils operativ behandelt wurden. Histologisch zeigten der initiale Befund sowie das erste Rezidiv mit einem Ki67-Index von weniger als 2 % aller Tumorzellen eine niedrige Proliferationsrate, während das zweite Rezidiv eine deutlich erhöhte Mitoseund Proliferationsrate aufwies. Im Anschluss an die operative Behandlung führten wir hier eine Chemotherapie mit Carboplatin, Epirubicin und Cyclophosphamid durch. Zur Verlaufsbeobachtung wurde das gonadale Peptid Inhibin eingesetzt. AbstractWithin seven years our patient developed a granulosa cell tumor of the ovary which initially was treated surgically. Histologically, the initial finding as well as the first recurrence showed a low proliferation rate (Ki67 < 2 % of all tumor cells) whereas an increase of the mitotic and proliferation rate was observed (Ki67 > 30 %) in the second recurrence. After surgical treatment of this second recurrence we started a chemotherapy with carboplatine, epirubicine and cyclophosphamide. For monitoring treatment and detecting recurrence we used inhibin as tumor marker.

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The Relationship of p53 Accumulation and DNA Ploidy and Conventional Clinicopathological Prognostic Variables in Patients with Ovarian Carcinoma

Cited by 13 publications

References 27 publications

Image cytometry DNA ploidy correlates with histological subtypes in endometrial carcinomas

Image cytometry DNA ploidy correlates with histological subtypes in endometrial carcinomas

Histologic and immunohistochemical decision-making in endometrial adenocarcinoma

Zweites Rezidiv eines Granulosazelltumors mit verändertem Wachstumsmuster, erhöhter Mitoserate und Proliferationsindex

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