Pan-cytokeratin immunoexpression in Wilms' tumors: a simple approach for understanding tumor epithelial differentiation

Neves, José Ivanildo; Caballero, Otávia Luiza Damas de; Soares, Fernando Augusto

doi:10.1590/s1516-31802004000400011

Cited by 3 publications

(6 citation statements)

References 3 publications

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“…Not all cases contained sufficient tissue for all studies; overall wide-spectrum cytokeratin was performed in 44 cases, low molecular weight cytokeratin in 27 cases, synaptophysin in 37 cases, chromogranin A in 36 (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60) years old), and two older adults 460 years of age. The primary tumors were available for study in 36 cases; for eight patients only metastases (seven to lymph nodes, one to lung) were available.…”

Section: Methodsmentioning

confidence: 99%

“…Among the small round cell tumors, desmoplastic small round cell tumor and Wilms tumor routinely express cytokeratins, 45,46 and LMWCK, low molecular weight cytokeratin; WSCK, wide-spectrum cytokeratin. *: rare, positivity in o5% of tumor cells; 1+, positivity in 5-25% of tumor cells; 2+, positivity in 26-50% of tumor cells; 3+, diffuse positivity in 51% or more of tumor cells.…”

Section: The Cytokeratinsmentioning

confidence: 99%

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Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall

Bahrami

Gown²,

Baird³

et al. 2008

Modern Pathology

154

118

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Alveolar rhabdomyosarcoma may be extremely difficult to distinguish from other primitive round cell neoplasms without ancillary immunohistochemistry and/or genetic study. Particularly in adults and in the head and neck locations, the differential diagnosis of alveolar rhabdomyosarcoma includes small cell carcinoma and neuroepithelial tumors, such as esthesioneuroblastoma. We have recently seen cases of genetically confirmed alveolar rhabdomyosarcoma, which were misdiagnosed owing to expression of cytokeratins and neuroendocrine markers. We studied a large group of well-characterized alveolar rhabdomyosarcomas for expression of such markers. Forty-four alveolar rhabdomyosarcomas (18 genetically confirmed) were retrieved from our archives and immunostained for wide-spectrum cytokeratin (OSCAR), low molecular weight cytokeratin (Cam5.2), synaptophysin, chromogranin A, and CD56 using commercially available antibodies. Cases were scored as 'negative', 'rare' (o5% positive cells), '1 þ ' (5-25%), '2 þ ' (26-50%) and '3 þ ' (451%). The tumors occurred in 23 males and 21 females at a mean age of 18 years (range, o1-64 years), and involved many sites. Fifty percent of cases (22 of 44) expressed wide-spectrum cytokeratin, and scored almost equally as rare, 1 þ , and 2 þ , but rarely 3 þ . Cam5.2 was positive in 52% (14 of 27). Forty-three percent of cases (16 of 37) expressed at least one of the specific neuroendocrine markers, 32% (12 of 37) expressed synaptophysin, 22% (eight of 36) expressed chromogranin A, and 11% expressed both. Expression of synaptophysin and chromogranin A was typically confined to rare cells but could be more widespread. Thirty-two percent of cases (12 of 37) expressed the wide-spectrum cytokeratin and at least one of the neuroendocrine markers, and 8% (three of 36) expressed cytokeratin and both neuroendocrine markers. CD56 expression was nearly ubiquitous. Aberrant expression of epithelial and neuroendocrine markers is relatively common in alveolar rhabdomyosarcoma, occurring in 30-40% of cases. These findings have significant implications for the diagnosis of alveolar rhabdomyosarcoma, particularly in adults and in the head and neck locations. Although expression of cytokeratin and/or synaptophysin alone does not necessarily indicate epithelial or neuroendocrine differentiation, coexpression of cytokeratin and neuroendocrine markers, and in particular the presence of chromogranin expression, suggest true epithelial and/or neuroendocrine differentiation in a subset of alveolar rhabdomyosarcomas. CD56 is not a specific neuroendocrine marker, and should not be used in the absence of synaptophysin/chromogranin. These findings emphasize the need to employ a panel of markers, to include desmin, myogenin/MyoD1, and genetic study in the diagnosis of primitive round cell neoplasms in all age groups and in all locations.

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Section: Methodsmentioning

confidence: 99%

Section: The Cytokeratinsmentioning

confidence: 99%

Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall

Bahrami

Gown²,

Baird³

et al. 2008

Modern Pathology

154

118

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“…We showed that the most intense immunostaining comprising the darker half (0-130) of the entire greyscale spectrum (0-255) did not provide significant prognostic performance by any of the 33 calculated GLCM, fractal, and first-order statistical features. This result suggested the prognostic irrelevance of the differentiated epithelial cells with high cytokeratin expression [22]. All other intensity ranges offered 2-9 prognostically significant features, whereby moderate pixel intensity ranges (130-180) provided the best performance.…”

Section: Discussionmentioning

confidence: 92%

“…The rarity of intense staining was not due to the low number of epithelial cells, as specific staining covered on average 42.8% of the image area. It was previously shown that mature epithelial cells stain more intensely for cytokeratins in comparison to less differentiated cells [22,32]. Therefore, the rarity of intense pan cytokeratin immunostaining could be explained by the overwhelmingly low differentiation state of epithelial cells.…”

Section: Discussionmentioning

confidence: 97%

Analysis of Spatial Distribution and Prognostic Value of Different Pan Cytokeratin Immunostaining Intensities in Breast Tumor Tissue Sections

Vranes

Vujasinović

Rajković

et al. 2020

IJMS

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Cancer risk prognosis could improve patient survival through early personalized treatment decisions. This is the first systematic analysis of the spatial and prognostic distribution of different pan cytokeratin immunostaining intensities in breast tumors. The prognostic model included 102 breast carcinoma patients, with distant metastasis occurrence as the endpoint. We segmented the full intensity range (0–255) of pan cytokeratin digitized immunostaining into seven discrete narrow grey level ranges: 0–130, 130–160, 160–180, 180–200, 200–220, 220–240, and 240–255. These images were subsequently examined by 33 major (GLCM), fractal and first-order statistics computational analysis features. Interestingly, while moderate intensities were strongly associated with metastasis outcome, high intensities of pan cytokeratin immunostaining provided no prognostic value even after an exhaustive computational analysis. The intense pan cytokeratin immunostaining was also relatively rare, suggesting the low differentiation state of epithelial cells. The observed variability in immunostaining intensities highlighted the intratumoral heterogeneity of the malignant cells and its association with a poor disease outcome. The prognostic importance of the moderate intensity range established by complex computational morphology analyses was supported by simple measurements of its immunostaining area which was associated with favorable disease outcome. This study reveals intratumoral heterogeneity of the pan cytokeratin immunostaining together with the prognostic evaluation and spatial distribution of its discrete intensities.

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“…14,15 Mature epithelial tumour tubules can be highlighted by expression of specific keratins. 16 Experimentally, RA has been shown to be important in kidney development. 17 In a zebrafish nephrogenesis model systems it has been shown that RA plays a central role in differentiation and segmentation of the nephrons.…”

mentioning

confidence: 99%

Retinoic acid promotes differentiation of WiT49‐ but not of CCG99‐11 Wilms tumour cells

Jansson

Mengelbier

2023

Cancer Reports

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Background Most children with Wilms tumour are successfully treated with multidrug chemotherapy and surgery. These treatments cause severe side effects for the patients, an issue that needs to be addressed by exploring other treatment options with less or no side effects. One option is to complement current therapies with agents that could potentially induce tumour cell differentiation, for example retinoic acid (RA). Aims To facilitate quick assessment of an agent's effect on Wilms tumour differentiation by a rapid in vitro model system. Methods and Results Here WiT49 and CCG99‐11 Wilms tumour cells were treated with 10 μM RA for 72 h or 9 days. Cultured cells were scraped off from Petri dishes, pelleted and embedded in paraffin in the same way as clinical tumour specimens are preserved. Cell morphology and differentiation were evaluated by analyses of haematoxylin eosin (H&E) and immunohistochemical stainings. Based on H&E, WT1 and CKAE1/3 stainings, RA treatment induced further epithelial differentiation of WiT49 cells, whereas there was no sign of induced maturation in CCG99‐11 cells. Ki67 staining showed that RA inhibited cell proliferation in both cell lines. Conclusions Our study shows that in vitro culturing of WiT49 and CCG99‐11 cells, followed by pelleting and paraffin embedding of cell pellets, could aid in a quick evaluation of potential differentiating agents against Wilms tumour. In addition, our results strengthen previous results that retinoic acid could be a potential complement to regular Wilms tumour treatment.

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Pan-cytokeratin immunoexpression in Wilms' tumors: a simple approach for understanding tumor epithelial differentiation

Cited by 3 publications

References 3 publications

Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall

Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall

Analysis of Spatial Distribution and Prognostic Value of Different Pan Cytokeratin Immunostaining Intensities in Breast Tumor Tissue Sections

Retinoic acid promotes differentiation of WiT49‐ but not of CCG99‐11 Wilms tumour cells

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