Challenging Lung Carcinoma with Coexistent ΔNp63/p40 and Thyroid Transcription Factor-1 Labeling Within the Same Individual Tumor Cells

Pelosi, Giuseppe; Fabbri, Alessandra; Tamborini, Elena; Perrone, Francesco; Testi, Maria Adele; Settanni, Giulio; Busico, Adele; Centonze, Giovanni; Braidotti, Paola; Bulfamante, Gaetano; Braud, Filippo de; Garassino, Marina Chiara; Pastorino, Ugo

doi:10.1097/jto.0000000000000553

Cited by 22 publications

(46 citation statements)

References 5 publications

(4 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…They acquire heterogeneity and undergo differentiation during development, towards a phenotype that can be similar to that of Clara cell/pneumocytes II type, mixed (Clara cell/bronchial), superficial bronchial-epithelium-like or poorly differentiated, but always expressing TTF-1. As 80% of poorly differentiated carcinomas are positive for TTF-1, the authors suggest that the majority of them may derive from the peripheral alveolar epithelium of the TRU [20,21].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, two cases of NSCLCs with widespread and strong nuclear positivity for TTF-1 and p40 have been reported [21,22]. The authors speculate that these cases "could result from expression of stem/progenitor cell plasticity" [21]. Pelosi et al proposed the term "adenosquamous carcinoma or at least NSCLC with adenosquamous immunophenotype" for these cases [21], while Hayashi et al suggested that they could represent a "new under-recognized entity" [22].…”

Section: Discussionmentioning

confidence: 99%

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TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

et al. 2020

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TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (∆Np63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as "TTF-1+ p63+ adenocarcinoma". The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as "adenocarcinoma, solid variant", in keeping with the presence of TTF-1 expression and p40 negativity. A "wild type" genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these "basal-type tumors" like those in the better known "basal-like" cancer of the breast.Diagnostics 2020, 10, 25 2 of 9 characterized by predominantly solid growth, formed by cells with large, eosinophilic cytoplasm, with a misleading tendency to keratinization or a pseudosquamoid morphology. Thus, histochemical detection of mucin and immunohistochemistry are often essential tests in differential diagnosis of NSCLCs, expanding the routine morphological examination.The combined use of antibodies TTF-1 and cytokeratin 7 (CK7) for ADC and p63 with high molecular weight keratins (CK5/6) for SCC provides a very reliable distinction between these two subtypes of non-small-cell carcinoma [1,2]. Recently, p40 has been considered the most specific marker of SCC [3]. SCC shows positive immunostaining for CK5/6, p63 and p40 (∆Np63) (with strong and widespread nuclear reaction) and negative immunostaining for TTF-1 and CK7. In contrast, ADC shows positive immunostaining for TTF-1 and CK7 and negative immunostaining for p63, p40 and CK5/6 [3,4]. Even if few ADCs may stain positively for p63, they show only a focal and weak positivity [5], while CK5/6 and p40 expression is usually absent. CK5/6-positive immunostaining is very unusual in ADCs, and even if it is present, in the absence of p63 and p40, it is not sufficient to support the squamous differentiation [3][4][5][6]. For SCC, p63 and CK...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

et al. 2020

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“…The frequency of positivity for squamous markers in ADCs varies according to the panel of markers. For example, p40 and desmocollin show higher specificity for SQCC and lower positivity in ADC 15 , 16 . In the present study, we retrospectively examined consecutive small lung biopsies performed for lung cancer and used TTF1 and p63 as the main markers for ADC and SQCC, respectively.…”

Section: Discussionmentioning

confidence: 99%

Lung cancer biopsy: Can diagnosis be changed after immunohistochemistry when the H&E-Based morphology corresponds to a specific tumor subtype?

Bernardi¹,

Bernardi²,

Takagaki³

et al. 2018

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OBJECTIVES:Advancements in non-small cell lung cancer treatment based on targeted therapies have made the differentiation between adenocarcinoma and squamous cell carcinoma increasingly important. Pathologists are challenged to make the correct diagnosis in small specimens. We studied the accuracy of an immunohistochemical panel in subclassifying non-small cell lung cancer in routine small biopsies and compared the results with the diagnosis from resected lung specimens, autopsy samples or biopsied/resected metastases.METHODS:In total, 340 lung cancer biopsies were investigated for the expression of CK5, TTF1, p63 and surfactant.RESULTS:We characterized 166 adenocarcinomas and 124 squamous cell carcinomas. Overall, 85% of cases displayed binary staining (TTF1 positive/p63 negative, and vice versa). The diagnoses of ten cases with a morphology that indicated a specific tumor subtype were changed after immunohistochemistry (IHC). A second specimen was available for 71 patients, and the first diagnosis at biopsy was confirmed in 95% of these cases. Most non-small cell lung cancer cases present a binary immunohistochemical profile in small biopsies, contributing to good diagnostic accuracy with routine markers. In a small proportion of cases, the diagnosis can be changed after IHC even when the morphological aspects indicate one specific tumor subtype.CONCLUSIONS:We recommend that routine small biopsies of lung cancer without classic morphology should be subjected to a minimum immunohistochemical panel to differentiate adenocarcinoma from squamous cell carcinoma.

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“…However, Pelosi in 2015 4 and Hayashi in 2018 5 have both described unusual cases of NSCLC with co-expression of TTF1 and p40 in the same cells. Interestingly both cases have a similar molecular signature harboring TP53 mutation.…”

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confidence: 99%

When tumor doesn’t read textbook. Third case of TTF1 and p40 co-expression in the same tumour cells in a non-small cell carcinoma. A potential new entity to consider?

2019

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Summary Introduction The 2011 WHO Classification for lung adenocarcinoma enlightened the need for a wise use of immunohistochemistry to preserve tissue for both diagnosis and molecular studies. The current recommendation is to use a panel comprising TTF1 and p40 to classify tumors with no clear squamous or glandular differentiation as many studies have showed the higher specificity of p40 over p63 as marker of squamous differentiation. However, the co-expression of both markers opens a new scenario with subsequent classification and potentially treatment issues. Materials and methods We report a case of a non-small lung cell carcinoma (NSCLC) with coexistent expression of TTF1 and p40 in the same tumour cells. To our knowledge, this peculiar immunohistochemical profile is very rare, and thus a review of the clinical and molecular features including molecular variances of the tumour was performed. Review of the pertinent literature was also carried out. Results Two additional articles describing unusual cases of NSCLC with coexistent expression of TTF1 and p40 were found and compared to our case. Interestingly, they all carried out aberrant mutation in TP53 oncogene and were of advance stage. Conclusion The positivity for both “squamous” and “adenocarcinomatous” markers and mutations of TP53 could be the expression of a not fully recognized variant of NSCLC with possible implications for classification, diagnosis and therapy.

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Challenging Lung Carcinoma with Coexistent ΔNp63/p40 and Thyroid Transcription Factor-1 Labeling Within the Same Individual Tumor Cells

Cited by 22 publications

References 5 publications

TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

Lung cancer biopsy: Can diagnosis be changed after immunohistochemistry when the H&E-Based morphology corresponds to a specific tumor subtype?

When tumor doesn’t read textbook. Third case of TTF1 and p40 co-expression in the same tumour cells in a non-small cell carcinoma. A potential new entity to consider?

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