Expression pattern of ISL-1, TTF-1 and PAX5 in olfactory neuroblastoma

Abstract

Olfactory neuroblastoma (ONB) is a rare neoplasm of the sinonasal area with neuroendocrine differentiation. ISL-1, TTF-1 and PAX5 are transcription factors that are frequently upregulated in tumors showing neuroendocrine differentiation. The aim of our study was to evaluate these markers in a group of ONBs. We included 11 ONBs from 4 large university hospitals. Immunohistochemical expression of TTF-1, PAX5 and ISL-1 was evaluated. TTF-1, ISL-1 and PAX5 were expressed in 3/11 cases (27.27%, h-score: 3-45), 7/11 cases (63.64%, h-score: 23-200), and in 3/11 cases (27.77%, h-score 3-85), respectively. The patient with the strongest PAX5 reactivity exhibited an aggressive clinical course with rapid dissemination to the spine and death shortly after the diagnosis. No significant correlation in the expression of PAX5 and TTF-1 (ρ = 0.43; p = 0.18) was observed. ISL-1 is widely expressed in tumors with neuroendocrine differentiation and therefore of limited value in their differential diagnosis. TTF-1 positivity does not exclude the diagnosis of primary ONB, although usually only a small percentage of cells are positive. PAX5 expression is infrequent (27.27%) in ONB; however, if present it can be associated with a very aggressive clinical course.

Anterior Mediastinal Neuroblastoma Associated with Syndrome of Inappropriate Antidiuretic Hormone Secretion: A Morphologic, Immunohistochemical, and Genetic Case Report and Review of the Literature

“…14 The immunohistochemical staining for TdT and TTF1 are also unusual in neuroblastoma, though again, TTF1 positivity has been reported in up to 27% of olfactory neuroblastomas. 15…”

“…14 The immunohistochemical staining for TdT and TTF1 are also unusual in neuroblastoma, though again, TTF1 positivity has been reported in up to 27% of olfactory neuroblastomas. 15 Furthermore, PHOX2B has proven an excellent immunohistochemical marker of pediatric neuroblastoma with high sensitivity and specificity relative to other small round blue cell tumors encountered in childhood. However, up to 50% of adult neuroblastomas are negative for PHOX2B expression, as was seen in the current tumor, suggesting that these tumors may derive from a different progenitor cell.…”

The long noncoding RNA landscape of neuroendocrine prostate cancer and its clinical implications

“…In developmental biology, PAX5 is involved in B-cell differentiation and PAX9 in neural crest development. PAX5 has been observed as overexpressed in other neuroendocrine tumours [ 92 , 93 ], overexpressed in neuroblastoma [ 9 4 ], and shown to positively regulate c-Met transcription in small cell lung cancer [ 95 ]. In lung NETs, PAX6 is prognostic for aggressiveness [ 96 ].…”

Metastatic olfactory neuroblastoma: A small round blue cell puzzle on fine‐needle aspiration cytology

“…18 TTF-1, and PAX-5. 22 Without appropriate clinical and radiological information, the initial differential diagnosis derived from a SRBCT FNA specimen can be very wide, requiring ancillary tests to narrow down the list. That is especially true if the tumor does not reveal any secondary morphologic characteristics like muscle or neural differentiation, and if a SRBCT presents at a metastatic site.…”