Folate receptor alpha as an adjunct when the tubal lesion sits between STIL and STIC

Design

Retrospective immunohistochemical expression study across a lesion spectrum

Population

408 tubal epithelial samples from 262 patients, plus 30 high-grade serous carcinomas

Primary outcome

Proportion with folate receptor alpha percentage score 2+ or above, by lesion category

Effect

73.2% of STIC and 76.7% of HGSC high; STIL and earlier lesions predominantly low or negative

The distinction between a serous tubal intraepithelial lesion and a serous tubal intraepithelial carcinoma carries real consequence — it is the difference between a finding and a diagnosis of carcinoma in a risk-reducing salpingo-oophorectomy specimen — and it rests on morphology supported by p53 and Ki-67, which do not always resolve it.

Immunohistochemistry for folate receptor alpha was performed on 408 tubal epithelial samples from 262 patients, spanning normal tube, secretory cell expansions, secretory cell outgrowths, serous tubal intraepithelial lesions and carcinomas, with 30 high-grade serous carcinomas for comparison. Using a percentage score of 2+ or above, 73.2% of carcinomas in situ and 76.7% of invasive carcinomas scored high. Earlier lesions were predominantly low, negative or very low. Normal epithelium expressed it, but usually below the threshold — and less with increasing age.

The useful reading is directional. High folate receptor alpha supports the carcinoma end of the spectrum; low expression does not exclude it, because more than a quarter of confirmed carcinomas in this series did not reach the threshold. The authors position it explicitly as an adjunct to be read with morphology, p53 and Ki-67, which is the right claim for the numbers they have.

• Read it alongside p53 and Ki-67, never instead of them
• A high percentage score supports STIC; a low one does not exclude it
• Expression falls with age in normal epithelium — factor that into a low score in an older patient
• BRCA-mutated carcinomas expressed more than non-mutated ones, so germline status is context for the stain
• In most Indian laboratories this is a send-out, so reserve it for cases where the answer will change the report

Why it matters

It adds a stain to one of the few tubal diagnoses where the label alone changes a patient's cancer status.

Don't overread it

This is a cross-sectional expression study, not a diagnostic accuracy study against a reference standard with reported sensitivity and specificity. No cut-off has been validated prospectively.

The statistics, in plain English

73.2% of carcinomas scoring high means roughly one in four will be missed if the stain is used as a rule-out, which is why the authors call it adjunctive. The absence of a significant difference between carcinoma in situ and invasive carcinoma is the biologically interesting part — it says the change is established before invasion, so the stain cannot help you decide whether invasion has occurred.

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